Adipose-derived stem cells in the treatment of hepatobiliary diseases and sepsis

Determination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved.Adipose-derived mesenchymal stem cells(AD-MSC)are easily isolated and cultured for a long time before losing their stem cell characteristics,which are self-renewal and pluripotency.AD-MSC are mesenchymal stem cells that have pluripotent lineage characteristics.They are easily accessible,and the fraction of stem cells in the adipose tissue lysates is highest among all other sources of mesenchymal stem cells.It is also HLA-DR negative and can be transplanted allogenically without the need for immunosuppression.These advantages have popularized its use in many fields including plastic reconstructive surgery.However,in the field of hepatology and liver transplantation,the progress is slower.AD-MSC have the potential to modulate inflammation,ameliorate ischemia-reperfusion injury,and support liver and biliary tract regeneration.These are very important for the treatment of various hepatobiliary diseases.Furthermore,the anti-inflammatory potential of these cells has paramount importance in the treatment of sepsis.We need alternative therapeutic approaches to treat end-stage liver failure.AD-MSC can provide a means of therapy to bridge to definitive therapeutic alternatives such as liver transplantation.Here we propose to review theoretic applications of AD-MSC in the treatment of hepatobiliary diseases and sepsis.

Clinical Application Value of Combined Detection of CG and TBA in Differential Diagnosis of Hepatobiliary System Diseases

Objective: To understand the clinical value of combined detection of cholyglycine CG and TBA in differential diagnosis of hepatobiliary diseases. Methods: Serum samples from 50 healthy people were collected as healthy control group. According to the latest disease diagnosis and treatment plan, 58 cases of HBV asymptomatic carrier group, 17 cases of viral hepatitis group, 49 cases of cirrhosis group, 50 cases of primary liver cancer group and 50 cases of other hepatobiliary diseases groups were collected respectively. The concentration levels of cholyglycine and total bile acid in each group were detected, and the differences among each group were compared. Results: By statistical analysis, serum CG concentration in viral hepatitis group, cirrhosis group, primary liver cancer group and other hepatobiliary diseases group was significantly higher than that in asymptomatic HEPATITIS B carriers and healthy control group, the differences were statistically significant (p 0.05). There was no significant difference in CG concentration among viral hepatitis group, liver cirrhosis group, primary liver cancer group and other hepatobiliary diseases group (p > 0.05). The serum TBA levels of asymptomatic carriers, viral hepatitis group, cirrhosis group, primary liver cancer group and other hepatobiliary system diseases group were significantly higher than those of healthy control group, the difference was statistically significant, p 0.05. Conclusion: Serum CG expression can not only detect liver lesions, but also distinguish different liver lesions. The positive rate of CG combined with TBA detection in patients with hepatobiliary diseases is significantly higher than that of single CG index detection. CG combined with TBA detection can significantly improve the sensitivity and accuracy of the diagnosis of hepatobiliary diseases, which is worthy of popularization and application.

Bile acid indices as biomarkers for liver diseases I:Diagnostic markers

BACKGROUND Hepatobiliary diseases result in the accumulation of toxic bile acids(BA)in the liver,blood,and other tissues which may contribute to an unfavorable prognosis.AIM To discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile.METHODS We analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical analysis.The BA profile was characterized using BA indices,which quantifies the composition,metabolism,hydrophilicity,and toxicity of the BA profile.BA indices have much lower interand intra-individual variability compared to absolute concentrations of BA.In addition,BA indices demonstrate high area under the receiver operating characteristic curves,and changes of BA indices are associated with the risk of having a liver disease,which demonstrates their use as diagnostic biomarkers for cholestatic liver diseases.RESULTS Total and individual BA concentrations were higher in all patients.The percentage of secondary BA(lithocholic acid and deoxycholic acid)was significantly lower,while the percentage of primary BA(chenodeoxycholic acid,cholic acid,and hyocholic acid)was markedly higher in patients compared to controls.In addition,the percentage of taurine-amidation was higher in patients than controls.The increase in the non-12α-OH BA was more profound than 12α-OH BA(cholic acid and deoxycholic acid)causing a decrease in the 12α-OH/non-12α-OH ratio in patients.This trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic decompensation.The percentage of sulfation was also higher in patients with more severe forms of liver diseases.CONCLUSION BA indices have much lower inter-and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the risk of developing liver diseases.

Bile acid indices as biomarkers for liver diseases Ⅱ: The bile acid score survival prognostic model

BACKGROUND Cholestatic liver diseases are characterized by an accumulation of toxic bile acids(BA)in the liver,blood and other tissues which lead to progressive liver injury and poor prognosis in patients.AIM To discover and validate prognostic biomarkers of cholestatic liver diseases based on the urinary BA profile.METHODS We analyzed urine samples by liquid chromatography-tandem mass spectrometry and investigated the use of the urinary BA profile to develop survival models that can predict the prognosis of hepatobiliary diseases.The urinary BA profile,a set of non-BA parameters,and the adverse events of liver transplant and/or death were monitored in 257 patients with cholestatic liver diseases for up to 7 years.The BA profile was characterized by calculating BA indices,which quantify the composition,metabolism,hydrophilicity,formation of secondary BA,and toxicity of the BA profile.We have developed and validated the bile-acid score(BAS)model(a survival model based on BA indices)to predict the prognosis of cholestatic liver diseases.RESULTS We have developed and validated a survival model based on BA(the BAS model)indices to predict the prognosis of cholestatic liver diseases.Our results demonstrate that the BAS model is more accurate and results in higher truepositive and true-negative prediction of death compared to both non-BAS and model for end-stage liver disease(MELD)models.Both 5-and 3-year survival probabilities markedly decreased as a function of BAS.Moreover,patients with high BAS had a 4-fold higher rate of death and lived for an average of 11 mo shorter than subjects with low BAS.The increased risk of death with high vs low BAS was also 2-4-fold higher and the shortening of lifespan was 6-7-mo lower compared to MELD or non-BAS.Similarly,we have shown the use of BAS to predict the survival of patients with and without liver transplant(LT).Therefore,BAS could be used to define the most seriously ill patients,who need earlier intervention such as LT.This will help provide guidance for timely care for liver patients.CONCLUSION The BAS model is more accurate than MELD and non-BAS models in predicting the prognosis of cholestatic liver diseases.

Telomerase reactivation is associated with hepatobiliary and pancreatic cancers

Background:Human telomerase reverse transcriptase(hTERT)and its components play a significant role in cancer progression,but recent data demonstrated that telomeres and telomerase alterations could be found in other diseases;increasing evidence suggests a key role of this enzyme in the fields of hepatobiliary and pancreatic diseases.Data sources:We performed a PubMed search with the following keywords:telomerase,hepatocellular carcinoma,cholangiocarcinoma,pancreatic adenocarcinoma by December 2019.We reviewed the relevant publications that analyzed the correlation between telomerase activity and hepatobiliary and pancreatic diseases.Results:Telomerase reactivation plays a significant role in the development and progression of hepatobiliary and pancreatic tumors and could be used as a diagnostic biomarker for hepatobiliary and pancreatic cancers,as a predictor for prognosis and a promising therapeutic target.Conclusions:Our review summarized the evidence about the critical role of hTERT in cancerous and precancerous lesions of the alteration and its activity in hepatobiliary and pancreatic diseases.

Role of PIVKA-II in screening for malignancies at a hepatobiliary andpancreatic disease center: A large-scale real-world study

Background and aims:Protein induced by vitamin K absence or antagonist II(PIVKA-II)is a well-accepted biomarker for diagnosing hepatocellular carcinoma(HCC).Although nonspecific increase of PIVKA-II has been reported,real-world evidence remains scarce.Based on real-world data,this study aimed to comprehensively describe the use of PIVKA-II at a hepatobiliary and pancreatic disease center and to assess its utility for the initial screening of HCC or other hepatobiliary–pancreatic malignancies.Methods:This real-world retrospective study is based on the PIVKA-II results of 16,215 individuals and other relevant laboratory test(alpha-fetoprotein[AFP],carbohydrate antigen 19-9[CA19-9],liver function,blood coagulation indicators,hepatitis B virus,and hepatitis C virus).However,only the first PIVKA-II results of 7809 eligible individuals were included.Between-group comparisons,correlation analysis,and receiver operating characteristic curve analysis were performed.Results:PIVKA-II results were abnormal in patients with HCC(55.9%),biliary carcinoma(BC,13.4%),gastroin-testinal and pancreatic cancer(6.3%),and benign diseases(23.5%)as well as in healthy individuals(0.92%).The area under the curve of PIVKA-II for detecting malignancies was 0.7754(0.7620–0.7688),whereas that for detecting HCC was 0.7509(0.7357–0.7662).Stratifying the PIVKA-II values or combining PIVKA-II with AFP or CA19-9 helped improve the diagnostic performance of PIVKA-II for HCC.PIVKA-II values were significantly positively correlated with AST in patients with HCC and with bilirubin in patients with BC.Conclusions:This study determined the role of PIVKA-II in malignancy screening at hepatobiliary and pancreatic disease centers.It was also noted that the diagnostic efficacy of PIVKA-II for HCC improved after combining PIVKA-II with AFP or stratifying its value.