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Current Strategies for Quantitating Fibrosis in Liver biopsy

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Chinese Medical Journal 2015年第2期128卷 252-258页

作者： Yan Wang Jin-Lin Hou Department of Infectious Diseases State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Nanfang Hospital Southern Medical University Guangzhou Guangdong 510515 China Department of Hepatobiliary Surgery Zhujiang Hospital Southern Medical University Guangzhou Guangdong 510280 China

Objective：The present mini-review updated the progress in methodologies based on using Liver biopsy.Data Sources：Articles for study of liver fibrosis,Liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014.Study Selection：Key articles were selected mainly according to their levels of relevance to this topic and citations.Results：With the recently mounting progress in chronic liver disease therapeutics,comes by a pressing need for precise,accurate,and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients.Histopathological information is recognized as the most valuable data for fibrosis assessment.Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility.Morphometric assessment by computer assist digital image analysis,such as collagen proportionate area （CPA）,detects change of fibrosis amount in tissue section in a continuous variable,and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis.Due to its evident sensitivity to sampling variances,morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort.Combining state-of-art imaging technology and fundamental principle in Tissue Engineering,structure-based quantitation was recently initiated with a novel proof-of-concept tool,qFibrosis.qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis,but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging.Conclusions：With input from multidisciplinary innovation,Liver biopsy assessment as a new ＂gold standard＂ is anticipated to substantially support the accelerated progress of Hepatology medicine.

关键词： Chronic liver Disease Cirrhosis Hepatic Fibrosis Liver biopsy Quantitative Assessment

Update on endoscopic ultrasound-guided Liver biopsy

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World Journal of Gastroenterology 2022年第28期28卷 3586-3594页

作者： Shiva Rangwani Devarshi R Ardeshna Khalid Mumtaz Sean G Kelly Samuel Y Han Somashekar G Krishna Division of Gastroenterology Hepatologyand NutritionDepartment of Internal MedicineOhio State University Wexner Medical CenterColumbusOH 43210United States

Endoscopic ultrasound guided Liver biopsy(EUS-LB)has emerged as a minimally-invasive alternative to the traditional(percutaneous or transjugular)Liver biopsy techniques for the diagnosis of liver parenchymal diseases.Potentially,EUS-LB combines the advantages of percutaneous and transjugular Liver biopsy in addressing focused sampling in addition to measuring portal pressure.Additionally,EUS-LB facilitates access to both the lobes of the liver which is not considered with the traditional percutaneous Liver biopsy.Multiple studies have compared EUS-LB with conventional Liver biopsy and reported comparable diagnostic yield,increased acquisition of complete portal tracts,and longer specimen length as compared to the traditional approaches.EUS-LB is associated with lesser post-procedural pain and shorter recovery time,while providing lower risk of complications when compared to traditional Liver biopsy.Innovations in needle types,needle sizes and suction techniques have aimed at further optimizing the EUS-LB technique.This review article updates current literature with focus on the variations in the technique and equipment used for EUS-LB,and compares EUS-LB with traditional methods of Liver biopsy.

关键词： Endoscopic ultrasound guided Liver biopsy Liver biopsy Percutaneous Liver biopsy Transjugular Liver biopsy liver parenchymal disease Portal pressure gradient

Endoscopic ultrasound guided Liver biopsy: Recent evidence

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World Journal of Gastrointestinal Endoscopy 2020年第3期12卷 83-97页

作者： Kemmian D Johnson Passisd Laoveeravat Eric U Yee Abhilash Perisetti Ragesh Babu Thandassery Benjamin Tharian Department of Internal Medicine Louisiana State University Health Sciences CenterNew OrleansLA 70112United States Department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTX 79430United States Department of Pathology College of MedicineUniversity of Arkansas for Medical SciencesLittle RockAR 72205United States Department of Internal Medicine Division of GastroenterologyUniversity of Arkansas for Medical SciencesLittle RockAR 72205United States Department of Internal Medicine Division of GastroenterologyCentral Arkansas Veterans Health Care SystemLittle RockAR 72205United States

Liver biopsy(LB)is an essential tool in diagnosing,evaluating and managing various diseases of the liver.As such,histopathological results are critical as they establish or aid in diagnosis,provide information on prognosis,and guide the appropriate selection of medical therapy for patients.Indications for LB include evaluation of persistent elevation of liver chemistries of unclear etiology,diagnosis of chronic liver diseases such as Wilson's disease,autoimmune hepatitis,small duct primary sclerosing cholangitis,work up of fever of unknown origin,amyloidosis and more.Traditionally,methods of acquiring liver tissue have included percutaneous LB(PCLB),transjugular LB(TJLB)or biopsy taken surgically via laparotomy or laparoscopy.However,traditional methods of LB may be inferior to newer methods.Additionally,PCLB and TJLB carry higher risks of adverse events and complications.More recently,endoscopic ultrasound guided LB(EUS-LB)has evolved as an alternative method of tissue sampling that has proven to be safe and effective,with limited adverse events.Compared to PC and TJ routes,EUS-LB may also have a greater diagnostic yield of tissue,be superior for a targeted approach of focal lesions,provide higher quality images and allow for greater patient comfort.These advantages have contributed to the increased use of EUS-LB as a technique for obtaining liver tissue.Herein,we provide a review of the recent evidence of EUS-LB for liver disease.

关键词： Liver biopsy Percutaneous Liver biopsy Transjugular Liver biopsy Endoscopic ultrasound guided Liver biopsy Fine-needle aspiration Core biopsy Fineneedle biopsy

Checkpoint inhibitor-induced hepatotoxicity:Role of Liver biopsy and management approach

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World Journal of Hepatology 2022年第7期14卷 1269-1276页

作者： Fernando Bessone Einar Stefan Bjornsson Department of Gastroenterology and Hepatology Facultad de Ciencias MédicasHospital Provincial del CentenarioUniversity of Rosario School of MedicineRosario 2000Santa FeArgentina Department of Gastroenterology Natl Univ Hosp IcelandSect Gastroenterol&HepatolDept Internal MedHringbraut 11DIS-101 ReykjavikIceland Landspitali University Hospital and Faculty of Medicine University of IcelandReykjavik Postal code 101State of ReykjavikIceland

Immunological checkpoint inhibitors(ICIs)have revolutionized therapy of many different malignanices.Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin,lungs,gastrointestinal and endocrine organs as well as the liver.liver injury has been reported in 3%-8%of patients with grade III-IV hepatitis in retrospective studies.The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation.The role for Liver biopsy(LB)in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management.LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected.Although there are no distinctive histological features,the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs.The natural history of hepatotoxicity of ICI therapy is not well known.Recent studies have demonstrated that 33%-50%of patients improve spontaneously with discontinuation of ICIs.In patients with jaundice and/or coagulopathy corticosteroids are used.The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial.Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens.Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.

关键词： Hepatotoxicity Checkpoint inhibitors Biologics hepatitis Drug-induced liver injury Liver biopsy

Endoscopic retrograde cholangiopancreatography and Liver biopsy in the evaluation of elevated liver function tests after liver transplantation

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World Journal of Hepatology 2021年第1期13卷 132-143页

作者： Augustin Attwell Samuel Han Michael Kriss Department of Medicine University of Colorado-DenverDenverCO 80203United States Department of Medicine Ohio State University Wexler Medical SchoolColumbusOH 43210United States Department of Medicine University of Colorado Medical SchoolAuroraCO 80045United States

BACKGROUND Abnormal liver function tests(LFTs)in post-liver transplant(LT)patients pose a challenge in the timing and selection of diagnostic modalities.There are little data regarding the accuracy of endoscopic retrograde cholangiopancreatography(ERCP)and Liver biopsy(LB)in diagnosing post-transplant complications.AIM To evaluate the diagnostic performance of ERCP and LB in patients with nonvascular post-LT complications.METHODS This single-center retrospective study evaluated patients undergoing both ERCP and LB for evaluation of elevated LFTs within 6 mo of LT from 2000 to 2017.Diagnostic operating characteristics including accuracy,sensitivity and specificity for various diagnoses were calculated for ERCP and LB.The R factor(ratio of alkaline phosphatase to alanine aminotransferase)was also calculated for each patient.RESULTS Of the 1284 patients who underwent LT,91 patients(74.7%males,mean age of 51)were analyzed.Anastomotic strictures(AS,24.2%),acute cellular rejection(ACR,11%)and concurrent AS/ACR(14.3%)were the most common diagnoses.ERCP carried an accuracy of 79.1%(95%CI:69.3-86.9),LB had an accuracy of 93.4%(95%CI:86.2-97.5),and the combination of the two had an accuracy of 100%(95%CI:96-100).There was no difference between patients with AS and ACR in mean R factor(AS:1.9 vs ACR:1.1,P=0.24).Adverse events did not differ between the two tests(ERCP:3.1%vs LB:1.1%,P=0.31).CONCLUSION In patients with abnormal LFTs after LT without vascular complications,the combination of LB and ERCP carries low risk and improves diagnostic accuracy over either test alone.

关键词： liver transplantation Endoscopic retrograde cholangiopancreatography Liver biopsy Abnormal liver tests Acute cellular rejection Anastomotic biliary stricture

Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by Liver biopsy

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World Journal of Hepatology 2016年第16期8卷 673-684页

作者： Maria Nicoline Baandrup Kristiansen Sanne Skovgard Veidal Kristoffer Tobias Gustav Rigbolt Kirstine Sloth Tolbol Jonathan David Roth Jacob Jelsing Niels Vrang Michael Feigh Niels Vrang Michael FeighGubra Aps Intercept Pharmaceuticals Inc.

AIM:To characterize development of diet-induced nonalcoholic steatohepatitis(NASH)by performing live biopsy in wild-type and genetically obese mice.METHODS:Male wild-type C57BL/6J(C57)mice(DIO NASH)and male Lep ob/Lep ob(ob/ob)mice(ob/ob-NASH were maintained on a diet high in trans-fat(40%)fructose(22%)and cholesterol(2%)for 26 and 12 wk respectively.A normal chow diet served as control in C57 mice(lean chow)and ob/ob mice(ob/ob chow)After the diet-induction period,mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted.Mice were then stratified into groups counterbalanced for steatosis score and fibrosi stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk.Global gene expression in liver tissue was assessed by RNA sequencing and bioin formatics.Metabolic parameters,plasma liver enzyme and lipids(total cholesterol,triglycerides)as well a hepatic lipids and collagen content were measured b biochemical analysis.Non-alcoholic fatty liver disease activity score(NAS)(steatosis/inflammation/ballooningdegeneration)and fibrosis were scored.Steatosis and fibrosis were also quantified using percent fractional area.RESULTS:Diet-induction for 26 and 12 wk in DIONASH and ob/ob-NASH mice,respectively,elicited progressive metabolic perturbations characterized by increased adiposity,total cholesterol and elevated plasma liver enzymes.The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis.Overall,the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice.During the eight week repeated vehicle dosing period,the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation.Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice(0 vs4.7±0.4,P<0.001 compared to lean chow)and ob/ob-NASH mice(2.4±0.3 vs 6.3±0.2,P<0.001compared to ob/ob chow),respectively.Furthermore,fibrosis stage was

关键词： Nonalcoholic steatohepatitis Liver biopsy Diet-induced obesity Nonalcoholic fatty liver disease Fibrosis

biopsy of solid liver tumors:adverse consequences

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Hepatobiliary & Pancreatic Diseases International 2008年第3期7卷 325-327页

作者： Dhya Al-Leswas Derek A O'Reilly Graeme J Poston Department of Surgery University Hospital Aintree Lower LaneLiverpoolL9 7ALUK

BACKGROUND:Percutaneous radiologically-guided Liver biopsy is used routinely worldwide in all secondary- level hospital centers.While it has an undoubted role in the investigation and management of acute and chronic inflammatory conditions of the liver,its role in hepatic oncology is doubtful and probably dangerous. METHOD:We report on two patients who underwent preoperative biopsy of potentially resectable liver tumors. RESULTS:At the time of surgery,there was evidence of seeding at the biopsy site in both cases.In case 1,potentially curative liver resection was rendered incurable because of gross peritoneal carcinomatosis lying adjacent to the site of Liver biopsy.In case 2,the patient underwent curative liver resection,but there was histopathological evidence of peritoneal disease beyond the liver capsule along the falciform ligament at the site of the previous biopsy. CONCLUSIONS:No patient with a suspicious liver tumor which is thought to be malignant and has any possibility of being a potential candidate for liver surgery,should be subjected to pre-operative diagnostic biopsy in a non- specialist center.

关键词： Liver biopsy colorectal liver metastases hepatocellular carcinoma

FibroScan-aspartate transaminase:A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

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World Journal of Gastroenterology 2024年第18期30卷 2440-2453页

作者： Jing-Ya Yin Tian-Yuan Yang Bing-Qing Yang Chen-Xue Hou Jun-Nan Li Yue Li Qi Wang Center of liver Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of Pathology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Beijing institute of infectious disease Beijing 100015China Beijing Key Laboratory of Emerging Infectious Diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijing 100015China

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to Liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via Liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnostic efficacy,i

关键词： Metabolic dysfunction-associated steatotic liver disease High-risk metabolic dysfunction-associated steatohepatitis Non-invasive models Liver biopsy Diagnostic value

Is endoscopic ultrasound a promising technique in the diagnosis and treatment of liver diseases?

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World Journal of Gastroenterology 2024年第22期30卷 2920-2922页

作者： Enver Zerem Željko Puljiz Boris Zdilar Suad Kunosic Admir Kurtcehajic Omar Zerem Department of Medical Sciences The Academy of Sciences and Arts of Bosnia and HerzegovinaSarajevo 71000Sarajevo CantonBosnia and Herzegovina Department of Gastroenterology and Hepatology University Clinical Center SplitSplit 21000Croatia Department of Medicine Croatian Military AcademyZagreb 10000Croatia Department of Physics Faculty of Natural Sciences and MathematicsUniversity of TuzlaTuzla 75000Tuzla KantonBosnia and Herzegovina Department of Gastroenterology and Hepatology Blue Medical GroupTuzla 75000Tuzla KantonBosnia and Herzegovina Department of Internal Medicine Cantonal Hospital“Safet Mujić”MostarMostar 88000Bosnia and Herzegovina

Percutaneous ultrasound has been a longstanding method in the diagnostics and interventional procedures of liver diseases.In some countries,its use is restricted to radiologists,limiting access for other clinicians,such as gastroenterologists.Endoscopic ultrasound,as a novel technique,plays a crucial role in diagnosis and treatment of digestive diseases.However,its use is sometimes recommended for conditions where no clear advantage over percutaneous ultrasound exists,leaving the impression that clinicians sometimes resort to an endoscopic approach due to the unavailability of percutaneous options.

关键词： Endoscopic ultrasound Percutaneous ultrasound Liver biopsy Fine needle aspiration Focal liver lesion liver abscess drainage