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Shunting branch of portal vein and stent position predict survival after transjugular intrahepatic portosystemic shunt

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World Journal of Gastroenterology 2014年第3期20卷 774-785页

作者： Ming Bai Chuang-Ye He Xing-Shun Qi Zhan-Xin Yin Jian-Hong Wang Wen-Gang Guo Jing Niu Jie-Lai Xia Zhuo-Li Zhang Andrew C Larson Kai-Chun Wu Dai-Ming Fan Guo-Hong Han department of liver Disease and department of digestive Interventional Radiology Xijing Hospital of Digestive DiseasesFourth Military Medical University department of Ultrasound Xijing Hospital of Digestive Diseases department of Medical Statistics Fourth Military Medical University department of Radiology Northwestern University department of Radiology Xijing Hospital Xijing Hospital of digestive diseases

AIM:To evaluate the effect of the shunting branch of the portal vein(PV)(left or right)and the initial stent position(optimal or suboptimal)of a transjugular intrahepatic portosystemic shunt(TIPS).METHODS:We retrospectively reviewed 307 consecu5tive cirrhotic patients who underwent TIPS placement for variceal bleeding from March 2001 to July 2010 at our center.The left PV was used in 221 patients and the right PV in the remaining 86 patients.And,224 and83 patients have optimal stent position and sub-optimal stent positions,respectively.The patients were followed until October 2011 or their death.Hepatic encephalopathy,shunt dysfunction,and survival were evaluated as outcomes.The difference between the groups was compared by Kaplan-Meier analysis.A Cox regression model was employed to evaluate the predictors.RESULTS:Among the patients who underwent TIPS to the left PV,the risk of hepatic encephalopathy(P=0.002)and mortality were lower(P<0.001)compared to those to the right PV.Patients who underwent TIPS with optimal initial stent position had a higher primary patency(P<0.001)and better survival(P=0.006)than those with suboptimal initial stent position.The shunting branch of the portal vein and the initial stent position were independent predictors of hepatic encephalopathy and shunt dysfunction after TIPS,respectively.And,both were independent predictors of survival.CONCLUSION:TIPS placed to the left portal vein with optimal stent position may reduce the risk of hepatic encephalopathy and improve the primary patency rates,thereby prolonging survival.

关键词： Transjugular intrahepatic portosystemic shunt Cirr

miR-222 targets ACOX1, promotes triglyceride accumulation in hepatocytes

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Hepatobiliary & Pancreatic diseases International 2019年第4期18卷 360-365页

作者： Jing-Jie Wang Yi-Tong Zhang Yu Jen Tseng Jun Zhang department of digestive diseases Huashan Hospital Fudan University

Background:Non-alcoholic fatty liver disease(NAFLD)is one of the most prevalent chronic liver diseases.However,the exact pathogenesis of NAFLD remains to be elucidated.Despite the association with tumors and cardiovascular diseases,the role of miR-222 in NAFLD remains unclear.The present study was to investigate the role of miR-222 in NAFLD.Methods:Wild-type C57BL/6 mice were fed a high-fat diet for 12 weeks to induce NAFLD.Normal human liver cell line(L02)was cultured with free fatty acid(FFA)-containing medium to stimulate cell steatosis.The mRNA levels of miR-222 and acyl Coenzyme A xidase 1(ACOX1)were detected by quantitative-PCR(Q-PCR).The prediction of ACOX1 as the target gene for miR-222 was conducted via TargetScan.The overexpression or inhibition of miR-222 was mediated by miR-222 mimics or antagomir,and intracellular triglyceride levels were measured using a triglyceride kit.Luciferase reporter assays verified ACOX1 as the target gene for miR-222.Results:miR-222 was significantly elevated in both the in vivo and in vitro NAFLD models.Overexpression of miR-222 significantly increased triglyceride content in the L02 cells,while inhibition of miR-222 expression restricted the accumulation of triglyceride.Overexpression of miR-222 significantly inhibited ACOX1 expression.Transient transfection assays verified that ACOX1 3-UTR luciferase reporter activity could be inhibited by miR-222 overexpression.Conclusions:The present study suggested that miR-222 promotes the accumulation of triglycerides by inhibiting ACOX1.

关键词： ACOX1 Hepatocyte steatosis miR-222 NAFLD β-hydroxybutyrate

β-arrestin 2 attenuates lipopolysaccharide-induced liver injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation in mice

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World Journal of Gastroenterology 2018年第2期24卷 216-225页

作者： Meng-Ping Jiang Chun Xu Yun-Wei Guo Qian-Jiang Luo Lin Li Hui-Ling Liu Jie Jiang Hui-Xin Chen Xiu-Qing Wei department of digestive diseases The Third Affiliated Hospital of Sun Yat-sen University department of digestive diseases Huizhou Municipal Center Hospital

AIM To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide(LPS)-induced liver injury in vivo and in vitro.METHODS Male β-arrestin 2^(+/+) and β-arrestin 2^(-/-)C57 BL/6 J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-κB signaling pathway.RESULTS Compared with wild-type mice, the β-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of proinflammatory cytokines, including interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and IL-10. Compared with the control group, pro-inflammatory cytokines(including IL-1β, IL-6, TNF-α, and IL-10) produced by RAW264.7 cells in the β-arrestin 2 si RNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-κB signaling pathway, including phosphoIκBα and phosho-p65, were upregulated.CONCLUSION β-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation.

关键词： Lipopolysaccharide liver injury β-arrestin 2 TLR4/NF-κB signaling pathway Pro-inflammatory cytokines

Biliary cholesterol secretion: More than a simple ABC

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World Journal of Gastroenterology 2010年第47期16卷 5936-5945页

作者： Arne Dikkers Uwe JF Tietge department of Pediatrics Center for Liver Digestive and Metabolic DiseasesUniversity Medical Center Groningen University of Groningen

Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophysiological determinant of cholesterol gallstone formation. This review summarizes current knowledge on the origins of cholesterol secreted into the bile as well as the relevant processes and transporters involved. Next to the established ATP-binding cassette (ABC) transporters mediating the biliary secretion of bile acids (ABCB11), phospholipids (ABCB4) and cholesterol (ABCG5/G8), special attention is given to emerging proteins that modulate or mediate biliary cholesterol secretion. In this regard, the potential impact of the phosphatidylserine flippase ATPase class Ⅰ type 8B member 1, the Niemann Pick C1-like protein 1 that mediatescholesterol absorption and the high density lipoprotein cholesterol uptake receptor, scavenger receptor class B type Ⅰ, is discussed.

关键词： Cholesterol Bile Gallstone Atherosclerosis Reverse cholesterol transport Lipoproteins High density lipoprotein Scavenger receptor class B type Ⅰ

Mitochondrial Damage and Drp1 Overexpression in Rifampicin-and Isoniazid-induced liver Injury Cell Model

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Journal of Clinical and Translational Hepatology 2019年第1期7卷 40-45页

作者： Fangfang Li Juan Zhou Yi Li Kewei Sun Jun Chen department of liver diseases Third Hospital of ShenzhenShenzhenGuangdongChina department of digestive diseases First Hospital of ChenzhouChenzhouHunanChina department of Infectious diseases The Affiliated Zhuzhou Hospital Xiangya Medical College CSUZhuzhouHunanChina liver diseases Center Department of Infectious DiseasesThe Second Xiangya HospitalCentral South UniversityChangshaHunanChina department of Infectious diseases First Hospital of Hunan University of Chinese MedicineChangshaHunanChina

Background and Aims:Rifampicin(RFP)and isoniazid(INH)are widely used as anti-tuberculosis agents.However,the mechanisms underlying the involvement of reactive oxygen species and mitochondria in RFP-and INH-related hepatotoxicity have not been established yet.This study aimed to observe the intracellular mechanisms leading to mitochondrial dysfunction and morphological changes in RFP-and INH-induced hepatocyte injury.Methods:Cell injury,changes in mitochondrial function,and expression and activation of dynamin related protein 1(Drp1),known as the main protein for mitochondrial fission,were analyzed in cultured QSG7701 cells exposed to RFP and INH.Results:INH and RFP treatment induced pronounced hepatocyte injury and increased cell death.In the similar context of aspartate aminotransferase elevation and adenosine triphosphate synthesis decrease,changes in mitochondrial membrane permeability and reactive oxygen species in hepatocytes induced by RFP were significantly different from those induced by INH(p<0.05).Particularly,we observed the overactivation and mitochondrial translocation of Drp1 in RFP-induced cell injury,which was not occurred with exposure to INH.Conclusions:RFP-induced hepatotoxicity may be closely related to mitochondrial dysfunction and Drp1-mediated mitochondrial fission.

关键词： Anti-tuberculosis drug-induced liver injury Drp1 Mitochondrial dysfunction Mitochondrial fission

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第19期30卷 2512-2522页

作者： Juan Jose Urquijo-Ponce Carlos Alventosa-Mateu Mercedes Latorre-Sánchez Inmaculada Castelló-Miralles Moisés Diago Hepatology Unit department of digestive diseases Consorcio Hospital General Universitario of ValenciaValencia 46014Spain

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

关键词： Hepatocellular carcinoma Early stage Intermediate stage Neoadjuvant Adjuvant Systemic therapy

Prognostic factors in non-malignant and non-cirrhotic patients with portal cavernoma: An 8-year retrospective single-center study

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World Journal of Gastroenterology 2013年第42期19卷 7447-7454页

作者： Xing-Shun Qi Ming Bai Chuang-Ye He Zhan-Xin Yin Wen-Gang Guo Jing Niu Fei-Fei Wu Guo-Hong Han department of liver diseases and digestive Interventional Radiology Xijing Hospital of Digestive DiseasesFourth Military Medical University

AIM:To evaluate the outcome of non-malignant and non-cirrhotic patients with portal cavernoma and to determine the predictors for survival.METHODS:Between July 2002 and June 2010,we retrospectively enrolled all consecutive patients admitted to our department with a diagnosis of portal cavernoma without abdominal malignancy or liver cirrhosis.The primary endpoint of this observational study was death and cause of death.Independent predictors of survival were identified using the Cox regression model.RESULTS:A total of 64 patients were enrolled in the study.During a mean follow-up period of 18±2.41mo,7 patients died.Causes of death were pulmonary embolism(n=1),acute leukemia(n=1),massive esophageal variceal hemorrhage(n=1),progressive liver failure(n=2),severe systemic infection secondary to multiple liver abscesses(n=1)and accident(n=1).The cumulative 6-,12-and 36-mo survival rates were 94.9%,86%and 86%,respectively.Multivariate Cox regression analysis demonstrated that the presence of ascites(HR=10.729,95%CI:1.209-95.183,P=0.033)and elevated white blood cell count(HR=1.072,95%CI:1.014-1.133,P=0.015)were independent prognostic factors of non-malignant and non-cirrhotic patients with portal cavernoma.The cumulative 6-,12-and 36-mo survival rates were significantly different between patients with and without ascites(90%,61.5%and 61.5%vs 97.3%,97.3%and 97.3%,respectively,P=0.0008).CONCLUSION:The presence of ascites and elevated white blood cell count were significantly associated with poor prognosis in non-malignant and non-cirrhotic patients with portal cavernoma.

关键词： Extrahepatic portal vein obstruction Portal cavernoma Survival Prognostic factors Ascites

Resection vs.transplantation for hepatocellular carcinoma:a never ending challenge

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 443-446页

作者： Joana Ferrer-Fàbrega Jordi Bruix Barcelona Clínic liver Cancer Group(BCLC) IDIBAPSBarcelonaSpain Hepatic Oncology Unit Hospital ClínicBarcelonaSpain Hepatobiliopancreatic Surgery and liver and Pancreatic Transplantation Unit Department of SurgeryInstitute Clínic of Digestive and Metabolic Diseases(ICMDiM)Hospital ClínicBarcelonaSpain department of Medicine and Departament of Surgery University of BarcelonaBarcelonaSpain CIBERehd BarcelonaSpain liver Unit Institute Clínic of Digestive and Metabolic Diseases(ICMDiM)Hospital ClínicBarcelonaSpain

liver transplantation(LT)is fully established in conventional clinical care for patients with hepatocellular carcinoma(HCC).The long-term survival of transplanted patients competes with the survival offered by surgical resection and this sets the scene for a debate for which a consensus answer based in evidence is not available.Resection outcomes have steadily improved due a refined selection of patients and the availability of other effective options such as ablation or locoregional approach(chemoembolization or radioembolization)has allowed to avoid its indication as a last effective resource for desperate cases.Same evolution has taken place for LT as it was early shown that if the tumor burden was reduced the survival results would be encouraging(1).

关键词： Hepatocellular carcinoma(HCC) liver resection liver transplantation(LT) survival recurrence

Assessing the Effectiveness of Strategies in US Birth Cohort Screening for Hepatitis C Infection

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Journal of Clinical and Translational Hepatology 2020年第1期8卷 25-41页

作者： Cynthia J.Tsay Joseph K.Lim department of Internal Medicine Yale University School of MedicineNew HavenCTUSA Yale liver Center Section of Digestive DiseasesYale University School of MedicineNew HavenCTUSA

Chronic hepatitis C infection in the USA is a highly morbid condition and current guidelines recommend one-time screening among the birth cohort(1945-1965).Understand-ing strategies to optimize screening can help inform future hepatitis C virus(HCV)screening guidelines.A focused literature search was performed using PubMed and manual abstract review from major hepatology conferences over the past 2 years.The search strategy involved using Medical Subject Headings terms for hepatitis C,screening,birth cohort,baby boomers,and 1945-1965.The review was limited to data from the USA.A total of 327 articles were identified and 36 abstracts were included,with studies published between 2012-2019.Strategies including clinician education,electronic medical record alerts,reflex HCV RNA testing,point-of-care testing,multisite(outpatient,inpatient,emergency department,endoscopy suite)initiatives,direct patient solicitation,and utilization of non-physician providers have increased HCV screening rates.However,broad imple-mentation remains less than optimal.Barriers include lack of patient acceptance to screening and engagement in the HCV care cascade.The Veterans Affairs Healthcare System has achieved higher birth cohort screening rates through an integrated approach requiring high-level engagement by leadership and institutional commitment.Multiple strategies for increasing birth cohort screening have been successful,but overall rates of HCV screening remain low.These strat-egies can inform public health efforts to implement emerging national recommendations for expansion of HCV screening to all U.S.adults age 18 or older.

关键词： Hepatitis C Epidemiology HCV antibody Screening Birth cohort Baby boomers Care cascade Electronic medical records