Road to recompensation:BavenoⅦcriteria and transjugular intrahepatic portosystemic shunt in liver cirrhosis

Liver cirrhosis has long been considered a point of no return,with limited hope for recovery.However,recent advancements,particularly the Baveno VII criteria and the utilization of transjugular intrahepatic portosystemic shunt(TIPS),have illuminated the concept of hepatic recompensation.In this editorial we comment on the article by Gao et al published in the recent issue.This editorial provides a comprehensive overview of the evolution of understanding cirrhosis,the criteria for recompensation,and the efficacy of TIPS in achieving recompensation.We discuss key findings from recent studies,including the promising outcomes observed in patients who achieved recompensation post-TIPS insertion.While further research is needed to validate these findings and elucidate the mechanisms underlying recompensation,the insights presented here offer renewed hope for patients with decompensated cirrhosis and highlight the potential of TIPS as a therapeutic option in their management.

Advancing hepatic recompensation:Baveno VII criteria and therapeutic innovations in liver cirrhosis management

The Baveno VII criteria redefine the management of decompensated liver cirrhosis,introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline.Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies,including antivirals and lifestyle modifications.Studies on alcohol,hepatitis C virus,and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes.Transjugular intrahepatic portosystemic shunt(TIPS)emerges as a promising intervention,effectively resolving complications of portal hypertension and facilitating recompensation.However,optimal timing and patient selection for TIPS remain unresolved.Despite challenges,TIPS offers renewed hope for hepatic recompensation,marking a significant advancement in cirrhosis management.Further research is needed to refine its implementation and maximize its benefits.In conclusion,TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.

Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study

BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and mortality.Despite its clinical importance,recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are lacking.AIM To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal rebleeding.METHODS This study included 477 EGVB patients across 2 cohorts:The derivation cohort(n=322)and the validation cohort(n=155).The primary outcome was rebleeding events within 1 year.The least absolute shrinkage and selection operator was applied for predictor selection,and multivariate Cox regression analysis was used to construct the prognostic model.Internal validation was performed with bootstrap resampling.We assessed the discrimination,calibration and accuracy of the model,and performed patient risk stratification.RESULTS Six predictors,including albumin and aspartate aminotransferase concentrations,white blood cell count,and the presence of ascites,portal vein thrombosis,and bleeding signs,were selected for the rebleeding event prediction following endoscopic treatment(REPET)model.In predicting rebleeding within 1 year,the REPET model ex-hibited a concordance index of 0.775 and a Brier score of 0.143 in the derivation cohort,alongside 0.862 and 0.127 in the validation cohort.Furthermore,the REPET model revealed a significant difference in rebleeding rates(P<0.01)between low-risk patients and intermediate-to high-risk patients in both cohorts.CONCLUSION We constructed and validated a new prognostic model for variceal rebleeding with excellent predictive per-formance,which will improve the clinical management of rebleeding in EGVB patients.

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.

Transjugular intrahepatic portosystemic shunt for recompensating decompensated cirrhosis?

Transjugular intrahepatic portosystemic shunt(TIPS)is a medical procedure that has been used to manage variceal bleeding and ascites in patients with cirrhosis.It can prevent further decompensation and improve the survival of high-risk decompensated patients.Recent research indicates that TIPS could increase the possibility of recompensation of decompensated cirrhosis when it is combined with adequate suppression of the causative factor of liver disease.However,the results of the studies have been based on retrospective analysis,and further validation is required by conducting randomized controlled studies.In this context,we highlight the limitations of the current studies and emphasize the issues that must be addressed before TIPS can be recommended as a potential recompensating tool.

External validation of EncephalApp Stroop test to screen minimal hepatic encephalopathy patients with nonalcoholic cirrhosis

BACKGROUND Neurocognitive impairment,including minimal hepatic encephalopathy(MHE)and overt hepatic encephalopathy,is one of the most common complications of all types of primary liver diseases,such as hepatitis B,biliary cholangitis,and autoi-mmune hepatitis.The EncephalApp Stroop test is a smartphone application-based test that is time-saving for MHE screening.However,neurocognitive impairment is different between alcoholic cirrhosis patients and nonalcoholic cirrhosis pa-tients,so the cutoff value for MHE diagnosis might be inflated.AIM To validate the Stroop test in nonalcoholic cirrhosis patients.METHODS This external validation was performed at the National Center for Infectious Diseases(Beijing).Liver cirrhosis patients aged between 18 and 65 years who voluntarily enrolled in the study and provided signed informed consent were included.The Psychometric Hepatic Encephalopathy Score(PHES)test was used as the standard diagnostic criterion for MHE.The EncephalApp Stroop test was then performed on the iPad,including two sessions of tests(“off”and“on”)to measure patients’ability to differentiate between numbers and letters.We assessed the performance of the EncephalApp Stroop test in terms of the area under the curve(AUC),sensitivity,specificity,positive predictive value,and negative predictive value,with the PHES as the standard criterion.RESULTS A total of 160 nonalcoholic cirrhosis patients were included in this validation study,including 87(54.4%)patients without MHE and 73(45.6%)patients with MHE.Taking the PHES as the gold standard,the EncephalApp Stroop test performed well for nonalcoholic liver cirrhosis patients in terms of“off”time[AUC:0.85,95%confidence interval(CI):0.79-0.91]and“on+off”time(AUC:0.85,95%CI:0.80-0.91);however,total runs of“off”session(AUC:0.61,95%CI:0.52-0.69),total runs of“on”session(AUC:0.57,95%CI:0.48-0.65),and“on–off”time(AUC:0.54,95%CI:0.44-0.63)were comparatively low.The optimal cutoff points were“off”time>101.93 seconds and“on+off”time>205.86 seconds,with sensitivities of 0.84 and 0.90,specificities of 0.77 and 0.71,positive predictive values of 0.75 and 0.72,and false-positive values of 0.85 and 0.89,respectively.CONCLUSION Our results suggest that different cutoffs should be used for the EncephalApp Stroop tool for MHE screening between alcoholic and nonalcoholic living patients,which is a critical check before generalization to screen for neurocognitive impairment among the whole population of chronic liver diseases.

Clinical review and literature analysis of hepatic epithelioid angiomyolipoma in alcoholic cirrhosis: A case report

BACKGROUND Hepatic epithelioid angiomyolipoma(HEA)has a low incidence and both clinical manifestations and imaging lack specificity.Thus,it is easy to misdiagnose HEA as other tumors of the liver,especially in the presence of liver diseases such as hepatitis cirrhosis.This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis,and analyzed the literature,in order to improve the understanding of this disease.CASE SUMMARY A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver.Based on the patient’s history,laboratory examinations,and imaging examinations,a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed.Postoperative pathology showed HEA.During outpatient follow-up,the patient showed no sign of recurrence.CONCLUSION HEA is difficult to make a definite diagnosis before surgery.HEA has the poten-tial for malignant degeneration.If conditions permit,surgical treatment is recom-mended.

Hepatitis C-related liver cirrhosis-strategies for the prevention of hepatic decompensation,hepatocarcinogenesis,and mortality

Liver cirrhosis (LC) is a critical stage of chronic liver disease, including that caused by hepatitis C virus (HCV). In the absence of antiviral therapy, 67%-91% of patients with HCV-related LC patients die of liver-related causes, including hepatocellular carcinoma (HCC) and liver failure. Among the therapeutic strategies used to prevent liver-related complications in these patients is standard therapy with pegylated interferon and ribavirin, which induces a sustained virological response (SVR) in 25% of HCV genotype 1-infected patients and in 69% of patients infected with genotypes 2 and 3. SVR in patients with HCV-related LC has been associated with reduced rates of hepatic decompensation, HCC, and mortality. More recently developed direct-acting antiviral agents have shown excellent antiviral efficacy, with preliminary data demonstrating that an interferon-free regimen that includes these direct-acting antiviral agents achieved SVR in more than 50% of patients with HCV genotype 1 LC. Branched-chain amino acid supplementation, improvement of insulin resistance, and the use of &#x003b2;-blockers for portal hypertension may also reduce liver-related complications. Here, we review advances in antiviral and adjunctive therapies for improved outcomes in patients with HCV-associated LC.

Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis

AIM: To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis (AL-LC).

Hepatic osteodystrophy and liver cirrhosis

AIM: To investigate the correlation between hepatic osteodystrophy and osteoporosis in patients with liver cirrhosis. METHODS: Bone mineral density of the patients (n = 55) and that of the control group (n = 30) were measured by dual-energy X-ray absorptiometry. All the women in the study were premenopausal. Deoxypyridinoline, pyridinoline and urinary Ca 2+ were measured as bone destruction markers, while alkaline phosphatase (ALP), osteocalcin and insulin-like growth factor-1 (IGF-1) were measured as bone formation markers. Furthermore, interleukin-1 (IL-1), IL-6, tumor necrosis factor α (TNF-α), vitamin D3, direct bilirubin, albumin, cortisol and parathyroid hormone (PTH) levels were measured. The independent Student t test and χ 2 test were employed in comparing both groups, and the Pearson correlation test was used to determine associations. RESULTS: Comparing cirrhosis and control groups, lumbar total T-score (-1.6 ± 1.2 g/cm 2 vs -0.25 ± 1.3 g/cm 2 , P < 0.001), lumbar total Z-score (-1.2 ± 1.23 g/cm 2 vs -0.6 ± 1.3 g/cm 2 , P < 0.001), total femur T-score (-0.05 ± 1 g/cm 2 vs -0.6 ± 0.9 g/cm 2 , P = 0.003) and total femur Z-score (-0.08 ± 1.5 g/cm 2 vs 0.7 ± 0.9 g/cm 2 , P =0.003) showed significantly lower values in the cirrhosis group. Blood ALP level (109.2 ± 57 U/Lvs 62.6 ± 32.5 U/L, P < 0.001), IL-6 level (27.9 ± 51.6 pg/mL vs 3.3 ± 3.1 pg/mL, P = 0.01), TNF-α level (42.6 ± 33.2 pg/mL vs 25.3 ± 12.3 pg/mL, P = 0.007) and direct bilirubin level (0.9 ± 0.7 mg/dL vs 0.3 ± 0.2 mg/dL, P < 0.001) were significantly higher in the cirrhosis group. IGF-1 level (47.7 ± 26.2 ng/mL vs 143.4 ± 53.2 ng/mL, P < 0.001), osteocalcin level (1.05 ± 2.5 ng/mL vs 7.0 ± 13 ng/mL, P = 0.002) and 24 h urinary Ca 2+ (169.6 ± 227.2 mg/dL vs 287 ± 168.6 mg/dL, P = 0.003) were significantly lower in the cirrhosis group. Urinary deoxypyridinoline/creatinine (9.4 ± 9.9 pmol/μmol vs 8.1 ± 5.3 pmol/μmol, P = 0.51), urinary pyridinoline/creatinine (51.3 ± 66.6 pmol/μmol vs 29 ± 25.8 pmol/μmol, P = 0.08), blood IL-1 level (3.4 ± 8.8 pg/mL vs 1.6 ± 3.5 pg/mL, P = 0.29), vitamin D3 level (18.6 ± 13.3 μg/L vs 18.4 ± 8.9 μg/L, P = 0.95), cortisol level (11.1 ± 4.8 μg/dL vs 12.6 ± 4.3 μg/dL, P = 0.15) and PTH level (42.7 ± 38 μg/dL vs 34.8 ± 10.9 μg/dL,P = 0.27) were not significantly different. CONCLUSION: Hepatic osteodystrophy is an important complication encountered in patients with liver cirrhosis and all patients should be monitored for hepatic osteodystrophy.

In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells(h UC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis.METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of h UC-MSCs. Histopathology was assessed by hematoxylin and eosin(H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR.RESULTS We demonstrated that the infused h UC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of h UC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION Transplanted h UC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. h UC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

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.

Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis

BACKGROUND Proton pump inhibitors(PPIs)are widely prescribed,often without clear indications.There are conflicting data on its association with mortality risk and hepatic decompensation in cirrhotic patients.Furthermore,PPI users and PPI exposure in some studies have been poorly defined with many confounding factors.AIM To examine if PPI use increases mortality and hepatic decompensation and the impact of cumulative PPI dose exposure.METHODS Data from patients with decompensated liver cirrhosis were extracted from a hospital database between 2013 to 2017.PPI users were defined as cumulative defined daily dose(cDDD)≥28 within a landmark period,after hospitalisation for hepatic decompensation.Cox regression analysis for comparison was done after propensity score adjustment.Further risk of hepatic decompensation was analysed by Poisson regression.RESULTS Among 295 decompensated cirrhosis patients,238 were PPI users and 57 were non-users.PPI users had higher mortality compared to non-users[adjusted HR=2.10,(1.20-3.67);P=0.009].Longer PPI use with cDDD>90 was associated with higher mortality,compared to non-users[aHR=2.27,(1.10-5.14);P=0.038].PPI users had a higher incidence of hospitalization for hepatic decompensation[aRR=1.61,(1.30-2.11);P<0.001].CONCLUSION PPI use in decompensated cirrhosis is associated with increased risk of mortality and hepatic decompensation.Longer PPI exposure with cDDD>90 increases the risk of mortality.

Transjugular intrahepatic portosystemic shunt in refractory chylothorax due to liver cirrhosis

A pleural effusion containing chylomicrons is termed chylothorax and results from leakage of lymph fluid into the pleural cavity.We report on the case of a 59-year-old woman with severe dyspnea due to a large chylothorax.She was known to have liver cirrhosis but no ascites.There was no history of trauma,cardiac function was normal and thorough diagnostic work-up did not reveal any signs of malignancy.In summary,no other etiology of the chylothorax than portal hypertension could be found.Therapy with diuretics as well as parenteral feeding failed to relieve symptoms.After a transjugular intrahepatic portosystemic shunt(TIPS) had successfully been placed,pleural effusion decreased considerably.Eight months later,TIPS revision had to be performed because of stenosis,resulting in remission from chylothorax.This case shows that even in the absence of ascites,chylothorax might be caused by portal hypertension and that TIPS can be an effective treatment option.

Hepatic encephalopathy in patients with liver cirrhosis:Is there a role of malnutrition?

Hepatic encephalopathy(HE) is a common complica-tion in patients with liver cirrhosis but its pathogenesis remains incompletely understood.Malnutrition is com-monly encountered in patients with liver cirrhosis and it has been reported to affect the quality of life of this group of patients.Experimental studies suggest that low energy intake and poor nutritional status may facil-itate the development of HE but there are scarce data on the potential role of malnutrition in HE in patients with liver cirrhosis.Two recently published studies have evaluated the potential role of malnutrition in the development of HE in cirrhotic patients with conflicting results.In this letter to the editor we briefly present the results of the two studies as well as potential rea-sons for the conflicting results reported.

Disturbance of hepatic and intestinal microcirculation in experimental liver cirrhosis

AIM: To analyze hepatic, mesenteric and mucosal microcirculation and leukocyte-endothelium interaction (LEI) in a rat model with liver cirrhosis.METHODS: Hepatic cirrhosis was induced in Wistar rats by gavage with carbon tetrachloride, and intravital videomicroscopy was performed in liver, mesentery and small intestine mucosa. Special emphasis is given on microcirculatory and morphometric changes during cirrhotic portal hypertension.RESULTS: LEI was influenced significantly in the cirrhotic liver but not in the gut. Blood flow measurement showed significant differences among liver, main mesenteric vessels and the mucosa. The results of our study indicate that liver cirrhosis leads to alterations in hepatic and mesenteric blood flow but not in mucosal blood flow.CONCLUSION: The enhanced inflammatory response in hepatic microvessels may be caused by a decrease of antithrombin Ⅲ levels and could be responsible for disturbances of organ pathology.

Sarcopenia and cognitive impairment in liver cirrhosis: A viewpoint on the clinical impact of minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) represents the mildest type of hepatic encephalopathy (HE). MHE is considered as a preclinical stage of HE and is part of a wide spectrum of typical neurocognitive alterations characteristic of patients with liver cirrhosis, particularly involving the areas of attention, alertness, response inhibition, and executive functions. MHE can be detected by testing the patients’ psychometric performance, attention, working memory, psychomotor speed, and visuospatial ability, as well as by means of electrophysiological and other functional brain measures. MHE is very frequent, affecting from 20% up to 80% of patients tested, depending of the diagnostic tools used. Although subclinical, MHE is considered to be clinically relevant. In fact, MHE has been related to the patients’ falls, fitness to drive, and working ability. As a consequence, MHE affects the patients and caregivers lives by altering their quality of life and even their socioeconomic status. Recently sarcopenia, a very common condition in patients with advanced liver disease, has been shown to be strictly related to both minimal and overt HE. Aim of this review is to summarize the most recently published evidences about the emerging relationship between sarcopenia and cognitive impairment in cirrhotic patients and provide suggestions for future research.

C–C motif chemokine ligand 16 inhibits the progression of liver cirrhosis via inactivating hepatic stellate cells

Background:Liver cirrhosis results from many forms of chronic damage,characterized by accumulation of extracellular matrix.The present study aimed to explore a potential non-invasive biomarker and its mechanism in the progression of liver cirrhosis.Methods:Gene Expression Omnibus(GEO)dataset(GSE15654,n=216)was analyzed to screen genes associated with progression of liver cirrhosis.A total of 181 plasma samples,including healthy control(HC,n=20),chronic hepatitis B(CHB,n=77)and HBV-related liver cirrhosis(LC,n=84),were enrolled for validation.In vitro and in vivo experiments were employed for the mechanistic investigation.Results:GEO dataset analysis showed that relatively low mRNA-expression of C–C motif chemokine ligand 16(CCL16)was associated with elevated Child-Pugh score(P=0.034)and worse prognosis(P=0.025).Plasma CCL16 level decreased in a stepwise pattern,with a median concentration of 10.29,6.57 and 4.47 ng/mL in the HC,CHB and LC groups,respectively(P<0.001).Low plasma CCL16 was significantly related to hepatic dysfunction both in the CHB and LC groups(P<0.05).Combination of CCL16 and ALT showed improved distinguishing capability for LC compared to either alone.In vitro,CCL16 expression was downregulated by lipopolysaccharide and hypoxia.Overexpression of CCL16 from human normal liver cell line(LO2)reduced the extracellular matrix associated proteins(Col1 and Col4)in human hepatic stellate cell line(LX-2).In vivo,the pathological feature of cirrhosis was alleviated by the hepatocytespecific expression of CCL16.Conclusions:CCL16 could be a feasible plasma marker to predict the occurrence and progression of liver cirrhosis.CCL16 might impact liver cirrhosis through inactivating hepatic stellate cells.

Effects of probiotic therapy on hepatic encephalopathy in patients with liver cirrhosis:an updated meta-analysis of six randomized controlled trials

BACKGROUND： Liver cirrhotic patients with hepatic encephalopathy have poor prognosis. Probiotics alter the intestinal microbiota and reduce the production of ammonia. We conducted a meta-analysis about the role of probiotics on liver cirrhotic patients with hepatic encephalopathy.DATA SOURCES： We collected the relevant literatures up to February 21, 2014 from databases of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. A statistical analysis was conducted by RevMan 5.2 and STATA 12.0 software.RESULTS： Six randomized controlled trials involving 496 liver cirrhotic patients were included. The results showed that probiotic therapy significantly reduced the development of overt hepatic encephalopathy（OR [95% CI]： 0.42 [0.26, 0.70],P=0.0007）. However, probiotics did not affect mortality, levels of serum ammonia and constipation（mortality： OR [95% CI]：0.73 [0.38, 1.41], P=0.35; serum ammonia： WMD [95% CI]：-3.67 [-15.71, 8.37], P=0.55; constipation： OR [95% CI]： 0.67 [0.29,1.56], P=0.35）.CONCLUSION： Probiotics decrease overt hepatic encephalopathy in patients with liver cirrhosis.

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.