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Bleeding risk and thrombosis in cirrhosis:a paradox with a need to address them

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 410-412页

作者： Anand V.Kulkarni K.Rajender Reddy Department of Hepatology Asian Institute of GastroenterologyHyderabadIndia Division of Gastroenterology and Hepatology University of PennsylvaniaPhiladelphiaPAUSA

Patients with cirrhosis have a state of“rebalanced hemostasis”where there is a simultaneous reduction in both qualitative and quantitative properties of procoagulants and anticoagulants,i.e.,platelets,fibrinogen,coagulation factors,protein C,S,and antithrombin and conversely,there is an increase in the levels of von Willebrand factor,endothelial factor VIII,tissue plasminogen activator(t-PA),and plasminogen activator inhibitor type 1(PAI-1)(1).Laboratory tests,such as INR,involving these coagulation proteins have been used for the prognostication of patients with cirrhosis/liver failure and have historically been part of several severity scores(2,3).Spontaneous bleeding due to clotting factor deficiencies is less frequent in the absence of mechanical trauma,while thrombosis is not uncommon and may merit anticoagulation therapy(4).However,the management of patients with cirrhosis with abnormalities in the hemostasis system is unclear.To meet this unmet need,the European Association for the Study of the liver(EASL)developed new guidelines for the prevention and management of bleeding and thrombosis in patients with cirrhosis(5).The bleeding here is referred to mucocutaneous and visceral bleeding events.

关键词： Viscoelastic tests international normalized ratio(INR) coagulation Liver disease

Minimum platelet count threshold before invasive procedures in cirrhosis:Evolution of the guidelines

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World Journal of Gastrointestinal Surgery 2023年第2期15卷 127-141页

作者： Marco Biolato Federica Vitale Tiziano Galasso Antonio Gasbarrini Antonio Grieco Department of Medical and Surgical Sciences CEMADFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy Department of Internal Medicine Catholic University of Sacred HeartRome 00168Italy

Cirrhotic patients with severe thrombocytopenia are at increased risk of bleeding during invasive procedures.The need for preprocedural prophylaxis aimed at reducing the risk of bleeding in cirrhotic patients with thrombocytopenia who undergo scheduled procedures is assessed via the platelet count;however,establishing a minimum threshold considered safe is challenging.A platelet count≥50000/μL is a frequent target,but levels vary by provider,procedure,and specific patient.Over the years,this value has changed several times according to the different guidelines proposed in the literature.According to the latest guidelines,many procedures can be performed at any level of platelet count,which should not necessarily be checked before the procedure.In this review,we aim to investigate and describe how the guidelines have evolved in recent years in the evaluation of the minimum platelet count threshold required to perform different invasive procedures,according to their bleeding risk.

关键词： Liver disease Thrombocytopenia Avatrombopag Lusutrombopag Transfusion

Chinese expert consensus on managing thrombocytopenia in patients with cancer and liver injury

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Oncology and Translational Medicine 2023年第1期9卷 1-14页

作者： Xianglin Yuan Committee of neoplastic supportive-care(CONS) China Anti-Cancer Association

Thrombocytopenia and liver injury are serious clinical problems in patients with cancer. The etiologyof thrombocytopenia in patients with cancer and liver injury (TCLI) is complicated. Managing cancertherapy-induced thrombocytopenia has gradually become standardized, and managing liver injuryassociatedthrombocytopenia has become more effective with the approval and marketing of relevantdrugs. However, the optimal strategy for managing thrombocytopenia in patients with cancer and liverinjury remains unclear, and the superposition of thrombocytopenia and liver injury further increasesthe difficulty of cancer treatment. Therefore, the Committee of Cancer Support Therapy of the ChineseAnti-Cancer Association has organized experts to analyze and discuss relevant literature to form aChinese expert consensus on managing thrombocytopenia in patients with cancer and liver injury(2022 Edition) to guide clinical practice.

关键词： cancer Liver disease liver injury thrombocytopenia expert consensus

Differential distribution of gene polymorphisms associated with hypercholesterolemia,hypertriglyceridemia,and hypoalphalipoproteinemia among Native American and Mestizo Mexicans

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World Journal of Hepatology 2022年第7期14卷 1408-1420页

作者： Rafael Torres-Valadez Sonia Roman Claudia Ojeda-Granados Karina Gonzalez-Aldaco Arturo Panduro Department of Genomic Medicine in Hepatology Civil Hospital of Guadalajara Fray Antonio Alcalde/Health Sciences CenterUniversity of GuadalajaraGuadalajaraJalisco 44280Mexico Unidad Especializada en Investigación Desarrollo e Innovación en Medicina Genómica Centro Nayarita de Innovación y Transferencia de TecnologíaUniversidad Autónoma de NayaritUnidad Académica de Salud IntegralTepicNayarit 63173Mexico

BACKGROUND Dyslipidemias are metabolic abnormalities associated with chronic diseases caused by genetic and environmental factors.The Mexican population displays regional differences according to ethnicity with an impact on the type of dyslipidemia.AIM To define the main dyslipidemias,the frequency of lipid-related risk alleles,and their association with hyperlipidemic states among different ethnic groups in West Mexico.METHODS In a retrospective study,1324 adults were selected to compare dyslipidemias and lipid-related gene polymorphisms.Demographic,clinical,and laboratory data were collected.A subgroup of 196 normal weight subjects without impaired glucose was selected for the association analyses.Genotyping was determined by allelic discrimination assay.RESULTS Hypercholesterolemia was the most prevalent dyslipidemia(42.3%).The frequency of the risk alleles associated with hypoalphalipoproteinemia(ABCA1)and hypercholesterolemia(APOE,LDLR)was higher in the Native Americans(P=0.047).In contrast,the Mestizos with European ancestry showed a higher frequency of the risk alleles for hypertriglyceridemia(APOE2,MTTP)(P=0.045).In normal weight Mestizo subjects,the APOB TT and LDLR GG genotypes were associated risk factors for hypercholesterolemia(OR=5.33,95%CI:1.537-18.502,P=0.008 and OR=3.90,95%CI:1.042-14.583,P=0.043,respectively),and displayed an increase in low-density lipoprotein cholesterol levels(APOB:β=40.39,95%CI:14.415-66.366,P=0.004;LDLR:β=20.77,95%CI:5.763-35.784,P=0.007).CONCLUSION Gene polymorphisms and dyslipidemias showed a differential distribution.Regional primary health care strategies are required to mitigate their prevalence considering the genetic and environmental features which could have important implications for personalized medicine within the new era of precision medicine.

关键词： Dyslipidemia Ethnicity Genes Obesity Lipids Liver disease Diet

Diagnosis of liver Involvement in Primary Sj(o)gren Syndrome

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Journal of Clinical and Translational Hepatology 2013年第2期1卷 94-102页

作者： Pilar Brito Zeron Soledad Retamozo Albert Bové Belchin Adriyanov Kostov Antoni Sisó Manuel Ramos-Casals Sj(o)gren Syndrome Research Group(AGAUR) Laboratory of Autoimmune Diseases Josep Font Institut d'Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS) Department of Autoimmune Diseases ICMiD Hospital Clinic Barcelona Spain Primary Care Research Group IDIBAPS Centre d'Assistència_Primària ABS Les Corts GESCLINIC Barcelona Spain

liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sj(o)gren syndrome (SS).In the 1990s,a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of Liver disease,liver function and a complete panel of autoantibodies.Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS.The most recent studies have shown that,after eliminating hepatotoxic drugs and fatty Liver disease,the two main causes of Liver disease in primary SS are chronic viral infections and autoimmune Liver diseases.The differential diagnosis of Liver disease in primary SS (viral vs autoimmune) is clinically important,since the two processes require different therapeutic approaches and have different prognoses.With respect to viral infections,chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area,while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries.After eliminating viral hepatitis,primary biliary cirrhosis (PBC) should be considered the main cause of Liver disease in primary SS.PBC-related SS patients may have a broad spectrum of abnormalities of the liver,including having no clinical or analytical data suggestive of Liver disease.Autoimmune hepatitis (AIH) is the second most frequently found autoimmune Liver disease to be associated with SS (all reported cases are type I),and nearly 10% of these patients have an AIH-PBC overlap.Finally,IgG4-related disease must be investigated in patients with SS presenting with sclerosing cholangitis,especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present.

关键词： Sj(o)gren syndrome Liver disease Hepatitis B virus Hepatitis C virus Primary biliary cirrhosis Autoimmune hepatitis Sclerosing cholangitis

Addition of statins to the standard treatment in patients with cirrhosis:Safety and efficacy

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World Journal of Gastroenterology 2021年第28期27卷 4639-4652页

作者： Alberto E Muñoz Florencia D Pollarsky Mónica Marino Mariano Cartier Horacio Vázquez Pablo Salgado Gustavo Romero Sección Hepatología Hospital de Gastroenterología Dr.Carlos Bonorino UdaondoFacultad de MedicinaUniversidad de Buenos AiresCiudad Autónoma de Buenos Aires 1264Argentina Instituto de Investigaciones en Salud Pública Facultad de OdontologíaUniversidad de Buenos AiresCiudad Autónoma de Buenos Aires 1122Argentina Unidad Clínica Hospital de Gastroenterología Dr.Carlos Bonorino UdaondoInvestigador Asociado del Gobierno de la Ciudad Autónoma de Buenos AiresCiudad Autónoma de Buenos Aires 1264Argentina

This review summarizes the safety and efficacy of statins in patients with cirrhosis.Due to concerns about the safety of statins in patients with impaired liver function,they have recently been investigated as a potential treatment option in cirrhosis.The most clinically significant adverse event is statin-related myopathy,and this may be related to the high serum statin concentrations in the setting of severely impaired liver function.Rhabdomyolysis is the most serious and potentially life-threatening manifestation.It has recently been demonstrated that the recommended dose of simvastatin in patients with decompensated cirrhosis would be 20 mg/d because higher values,such as 40 mg/d,are associated with many adverse events,especially muscle injury.Likewise,simvastatin should not be administered to patients with Model for End-stage Liver disease score>12 and/or Child-Pugh class C because of the high risk of severe muscle injury.Due to the pleiotropic effects,the focus on statins has shifted from being considered harmful to something useful.Through these effects,statins could prevent liver-related morbidity and mortality in cirrhotic patients.Observational studies in large populations of patients with cirrhosis have shown that treatment with statins to decrease high cholesterol levels was associated with a reduced risk of hepatic decompensation,hepatocellular carcinoma development and death.The few randomized controlled trials in patients with cirrhosis and portal hypertension showed that statins lower portal pressure,quite likely through a reduction in hepatic resistance.Another large randomized controlled trial in patients with variceal bleeding showed that simvastatin in addition to standard of care did not prevent rebleeding but improved survival rate.Despite these encouraging outcomes,the quality of the evidence regarding the use of statins is low or very low due to the observational characteristics of most of the studies involved.Therefore,it is advisable to perform further randomized controlled trials on a l

关键词： Cirrhosis Liver disease Statins Safety Efficiency

liver Transplantation Services During the Time of COVID-19

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Journal of Clinical and Translational Hepatology 2021年第4期9卷 587-591页

作者： Parita Patel Anjana Pillai Section of Gastroenterology Hepatologyand NutritionDepartment of Internal MedicineThe University of Chicago MedicineChicagoILUSA

The coronavirus disease 2019(COVID-19)is associated with high morbidity and mortality,prompting overwhelmed hospital systems to reallocate resources to those stricken with the disease.In response,many liver transplantation programs unexpectedly came to an abrupt halt,significantly affecting the lives of living donors and recipients around the world.As the risk-benefit scale of liver transplantation has changed in the era of COVID-19,it is prudent to understand the impact of COVID-19 on those with underlying Liver disease and those in need of a liver transplant.In this review,we discuss recommendations put forth by hepatology and transplant societies,summarize results from emerging studies,and propose strategies to appropriately risk stratify patients prior to transplantation.

关键词： COVID-19 liver transplantation Liver disease

Emerging roles of DJ-1 in Liver diseases through regulation of oxidative stress and immune response

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liver Research 2018年第2期2卷 87-91页

作者： Min Xu Lili Chen Jichang Li Hailong Wu Qiang Xia Xiaoni Kong Department of liver Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceInnovation Center for Cell Signaling NetworkInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina

Reactive oxygen species(ROS)and immune response play critical roles in the progression of liver diseases.DJ-1,also known as Parkinson disease 7(Park7),is extensively expressed in cells and tissues,where it governs numerous biological functions including chaperone activity,protease function,transcriptional and mitochondrial regulation,and ROS modulation.Moreover,we have established that DJ-1 plays a critical role in initiating an inflammatory response by modulating ROS generation.Therefore,DJ-1 may play an important role in the progression of Liver diseases by modulating ROS and the immune response.Recently,we have shown that DJ-1 deficiency negatively regulates proliferation of hepatic progenitor cells(HPCs)by impairing the formation of HPC-associated fibrosis and inflammatory niches.Deficiency of DJ-1 ameliorates liver fibrosis by inhibiting hepatic ROS production and inflammation;moreover,in a classic diethylnitrosamine(DEN)-mediated hepatocellular carcinoma(HCC)mouse model,deletion of DJ-1 ameliorates tumorigenesis and HCC cell proliferation by regulating hepatic inflammation and reducing the activity of the interleukin 6/signal transducer and activator of transcription 3(IL-6/STAT3)signaling pathway.Taken together,these data suggest a critical function for,and therapeutic value of,DJ-1 in treatment of Liver diseases.The aim of this review is to summarize these functions and the underlying molecular mechanisms of DJ-1 in Liver diseases,and to highlight the potential therapeutic value and future research direction of DJ-1 in Liver diseases.

关键词： DJ-1 Liver disease Oxidative stress Reactive oxygen species(ROS) Immune response

Therapeutic potential of stem cell in liver regeneration

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Frontiers of Medicine 2011年第1期5卷 26-32页

作者： Jinzheng LI Min LI Bolin NIU Jianping GONG Chongqing Key Laboratory of Hepatobiliary Surgery and Department of Hepatobiliary Surgery Second Affiliated HospitalChongqing Medical UniversityChongqing 400010China

liver transplantation is the only life-saving procedure for patients with end-stage Liver disease.However,its potential benefits are hampered by many disadvantages,such as the relative shortage of donors,operative risks,and high costs.These issues have prompted the search for new alternative therapies for irreversible Liver disease.Stem cell therapy,with the ability for self-renewal and potential for multilineage differentiation,is a promising alternative approach.Several studies have demonstrated that transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells leads to donor cell-mediated repopulation of the liver and improved survival rates in experimental models of Liver disease.However,a registered clinical application based on stem cell technology will take at least an additional 5 to 10 years because of some limitations;e.***.the lack of suitable cell sources and risk of teratoma formation.This review summarizes the general understanding of the therapeutic potentials of stem cells in Liver disease,including the sources,mechanisms,and delivery methods of hepatic stem cells in liver regeneration,and discusses some challenges for their therapeutic application.

关键词： stem cell Liver disease regenerative medicine