Evolution of the liver biopsy and its future.

Liver biopsies are commonly used to evaluate a wide variety of medical disorders, including neoplasms and post-transplant complications. However, its use is being impacted by improved clinical diagnosis of disorders, and non-invasive methods for evaluating liver tissue and as a result the indications of a liver biopsy have undergone major changes in the last decade. The evolution of highly effective treatments for some of the common indications for liver biopsy in the last decade (e.g., viral hepatitis B and C) has led to a decline in the number of liver biopsies in recent years. At the same time, the emergence of better technologies for histologic evaluation, tissue content analysis and genomics are among the many new and exciting developments in the field that hold great promise for the future and are going to shape the indications for a liver biopsy in the future. Recent advances in slide scanners now allow creation of "digital/virtual" slides that have image of the entire tissue section present in a slide [whole slide imaging (WSI)]. WSI can now be done very rapidly and at very high resolution, allowing its use in routine clinical practice. In addition, a variety of technologies have been developed in recent years that use different light sources and/or microscopes allowing visualization of tissues in a completely different way. One such technique that is applicable to liver specimens combines multiphoton microscopy (MPM) with advanced clearing and fluorescent stains known as Clearing Histology with MultiPhoton Microscopy (CHiMP). Although it has not yet been extensively validated, the technique has the potential to decrease inefficiency, reduce artifacts, and increase data while being readily integrable into clinical workflows. Another technology that can provide rapid and in-depth characterization of thousands of molecules in a tissue sample, including liver tissues, is matrix assisted laser desorption/ionization (MALDI) mass spectrometry. MALDI has already been applied in a clinical research setting with promising diagnostic and prognostic capabilities, as well as being able to elucidate mechanisms of liver diseases that may be targeted for the development of new therapies. The logical next step in huge data sets obtained from such advanced analysis of liver tissues is the application of machine learning (ML) algorithms and application of artificial intelligence (AI), for automated generation of diagnoses and prognoses. This review discusses the evolving role of liver biopsies in clinical practice over the decades, and describes newer technologies that are likely to have a significant impact on how they will be used in the future.

[1]  G. Menghini One-second needle biopsy of the liver. , 1958, Gastroenterology.

[2]  R. Fischer [Infectious diseases and the liver]. , 1960, Acta hepato-splenologica.

[3]  R. Perez-Tamayo Cirrhosis of the liver: a reversible disease? , 1979, Pathology annual.

[4]  Neil Kaplowitz,et al.  Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis , 1981, Hepatology.

[5]  W. Jiménez,et al.  Measurement of fibrosis in needle liver biopsies: Evaluation of a colorimetric method , 1985, Hepatology.

[6]  R. Falcone,et al.  Laparoscopic vs. open wedge biopsy of the liver. , 1993, Journal of laparoendoscopic surgery.

[7]  K. Batts,et al.  Use of fatty donor liver is associated with diminished early patient and graft survival. , 1996, Transplantation.

[8]  P. Bedossa,et al.  An algorithm for the grading of activity in chronic hepatitis C , 1996, Hepatology.

[9]  S. Y. Chuah,et al.  Liver biopsy--past, present and future. , 1996, Singapore medical journal.

[10]  C. Moorehead All rights reserved , 1997 .

[11]  D Chappard,et al.  Histopathological evaluation of liver fibrosis: quantitative image analysis vs semi-quantitative scores. Comparison with serum markers. , 1998, Journal of hepatology.

[12]  M. Sherman,et al.  Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis. , 2000, Archives of pathology & laboratory medicine.

[13]  M Masseroli,et al.  Automatic quantification of liver fibrosis: design and validation of a new image analysis method: comparison with semi-quantitative indexes of fibrosis. , 2000, Journal of hepatology.

[14]  M Masseroli,et al.  Liver fibrosis assessment with semiquantitative indexes and image analysis quantification in sustained-responder and non-responder interferon-treated patients with chronic hepatitis C. , 2001, Journal of hepatology.

[15]  C. Rigamonti,et al.  Evaluation of liver fibrosis in chronic hepatitis C with a computer-assisted morphometric method. , 2002, Annali italiani di medicina interna : organo ufficiale della Societa italiana di medicina interna.

[16]  J. Dienstag,et al.  The role of liver biopsy in chronic hepatitis C , 2002, Hepatology.

[17]  Salvador González,et al.  Evaluation of hepatic histology by near-infrared confocal microscopy: a pilot study. , 2002, Human pathology.

[18]  J. Fruit,et al.  The role of liver biopsy in chronic hepatitis C , 2002 .

[19]  Kevin W Eliceiri,et al.  Analysis of histology specimens using lifetime multiphoton microscopy. , 2003, Journal of biomedical optics.

[20]  V. Paradis,et al.  Sampling variability of liver fibrosis in chronic hepatitis C , 2003, Hepatology.

[21]  Scott L Nyberg,et al.  Assessment of donor liver steatosis: pathologist or automated software? , 2004, Human pathology.

[22]  Chen-Yuan Dong,et al.  Optical biopsy of liver fibrosis by use of multiphoton microscopy. , 2004, Optics letters.

[23]  Lennart Bodin,et al.  Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies: a comparison to stereological point counting , 2005, Modern Pathology.

[24]  O. Cummings,et al.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease , 2005, Hepatology.

[25]  Salvador González,et al.  In vivo and ex vivo virtual biopsy of the liver with near-infrared, reflectance confocal microscopy , 2005, Modern Pathology.

[26]  L. Miller,et al.  Simplified method of hepatic fibrosis quantification: design of a new morphometric analysis application , 2005, Liver international : official journal of the International Association for the Study of the Liver.

[27]  D. Jain,et al.  Liver Biopsy: Evolving Role in the New Millennium , 2005, Journal of clinical gastroenterology.

[28]  C. Mottin,et al.  A Comparison of Wedge and Needle Hepatic Biopsy in Open Bariatric Surgery , 2006, Obesity surgery.

[29]  D. Aguirre,et al.  Fatty liver: imaging patterns and pitfalls. , 2013, Radiographics : a review publication of the Radiological Society of North America, Inc.

[30]  A. Lièvre,et al.  KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. , 2006, Cancer research.

[31]  F. Carnot,et al.  Direct and indirect evidence for the reversibility of cirrhosis. , 2006, Human pathology.

[32]  Yukako Yagi,et al.  Primary histologic diagnosis using automated whole slide imaging: a validation study , 2006, BMC clinical pathology.

[33]  S. Friedman,et al.  Reversal of hepatic fibrosis — Fact or fantasy? , 2006, Hepatology.

[34]  A. Stavitsky,et al.  Differential contributions of C3, C5, and decay-accelerating factor to ethanol-induced fatty liver in mice. , 2007, Gastroenterology.

[35]  Vahid Mashayekhi,et al.  Feasibility and diagnostic agreement in teledermatopathology using a virtual slide system. , 2007, Human pathology.

[36]  Hanry Yu,et al.  Nonlinear optical microscopy: use of second harmonic generation and two-photon microscopy for automated quantitative liver fibrosis studies. , 2008, Journal of biomedical optics.

[37]  W. Kim,et al.  The global impact of hepatic fibrosis and end-stage liver disease. , 2008, Clinics in liver disease.

[38]  Tuya Shilagard,et al.  Visualizing hepatitis C virus infections in human liver by two-photon microscopy. , 2009, Gastroenterology.

[39]  R. Standish,et al.  Computer‐assisted image analysis of liver collagen: Relationship to Ishak scoring and hepatic venous pressure gradient , 2009, Hepatology.

[40]  H. Mani,et al.  Liver biopsy findings in chronic hepatitis B , 2009, Hepatology.

[41]  M. Manns,et al.  Clinical Relevance of Transjugular Liver Biopsy in Comparison with Percutaneous and Laparoscopic Liver Biopsy , 2009, Gastroenterology research and practice.

[42]  Christophe Odin,et al.  Fibrillar collagen scoring by second harmonic microscopy: a new tool in the assessment of liver fibrosis. , 2010, Journal of hepatology.

[43]  M. Lipp,et al.  Trends in the Indication and Method of Liver Biopsy for Hepatitis B and C , 2010, Digestive Diseases and Sciences.

[44]  S. Hazen,et al.  Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[S] , 2010, Journal of Lipid Research.

[45]  Mats Borén,et al.  Stopping the clock on proteomic degradation by heat treatment at the point of tissue excision , 2010, Proteomics.

[46]  Vladimir Hovhannisyan,et al.  Ex vivo imaging and quantification of liver fibrosis using second-harmonic generation microscopy. , 2010, Journal of biomedical optics.

[47]  Maxence Wisztorski,et al.  MALDI direct analysis and imaging of frozen versus FFPE tissues: what strategy for which sample? , 2010, Methods in molecular biology.

[48]  Hanry Yu,et al.  Assessment of liver steatosis and fibrosis in rats using integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique. , 2011, Journal of biomedical optics.

[49]  Jean-Michel Camadro,et al.  Imaging mass spectrometry provides fingerprints for distinguishing hepatocellular carcinoma from cirrhosis. , 2011, Journal of proteome research.

[50]  S. Bertrais,et al.  Steatosis degree, measured by morphometry, is linked to other liver lesions and metabolic syndrome components in patients with NAFLD , 2011, European journal of gastroenterology & hepatology.

[51]  K. Kultima,et al.  Biomarkers of disease and post-mortem changes - Heat stabilization, a necessary tool for measurement of protein regulation. , 2011, Journal of proteomics.

[52]  Cheng Ji,et al.  Metabonomic investigation of liver profiles of nonpolar metabolites obtained from alcohol-dosed rats and mice using high mass accuracy MSn analysis. , 2011, Journal of proteome research.

[53]  L. Hall,et al.  Performance and Cost Analysis of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Routine Identification of Yeast , 2011, Journal of Clinical Microbiology.

[54]  S. Rauser,et al.  MALDI imaging identifies prognostic seven-protein signature of novel tissue markers in intestinal-type gastric cancer. , 2011, The American journal of pathology.

[55]  L. Jeng,et al.  Direct tissue analysis by MALDI-TOF mass spectrometry in human hepatocellular carcinoma. , 2011, Clinica chimica acta; international journal of clinical chemistry.

[56]  Joachim M. Buhmann,et al.  Computational Pathology: Challenges and Promises for Tissue Analysis , 2015, Comput. Medical Imaging Graph..

[57]  Karuna Rasineni,et al.  Molecular mechanism of alcoholic fatty liver , 2012, Indian journal of pharmacology.

[58]  Horst Zitzelsberger,et al.  Tumor classification of six common cancer types based on proteomic profiling by MALDI imaging. , 2012, Journal of proteome research.

[59]  H. Dienes,et al.  The indications for liver biopsy. , 2012, Deutsches Arzteblatt international.

[60]  S. Richter,et al.  Evaluation of the Bruker Biotyper and Vitek MS Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Systems for Identification of Nonfermenting Gram-Negative Bacilli Isolated from Cultures from Cystic Fibrosis Patients , 2012, Journal of Clinical Microbiology.

[61]  Role of Percutaneous Liver Biopsy , 2012, Hepatitis monthly.

[62]  Y. N. Park,et al.  The Laennec staging system for histological sub-classification of cirrhosis is useful for stratification of prognosis in patients with liver cirrhosis. , 2012, Journal of hepatology.

[63]  Shuangmu Zhuo,et al.  Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions. , 2012, Journal of biomedical optics.

[64]  Nathan Heath Patterson,et al.  Histology-driven data mining of lipid signatures from multiple imaging mass spectrometry analyses: application to human colorectal cancer liver metastasis biopsies. , 2013, Analytical chemistry.

[65]  F. Cobo Application of MALDI-TOF Mass Spectrometry in Clinical Virology: A Review , 2013, The open virology journal.

[66]  Theodore Alexandrov,et al.  Imaging mass spectrometry reveals modified forms of histone H4 as new biomarkers of microvascular invasion in hepatocellular carcinomas , 2013, Hepatology.

[67]  S. Richter,et al.  Multicenter Evaluation of the Vitek MS Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry System for Identification of Gram-Positive Aerobic Bacteria , 2013, Journal of Clinical Microbiology.

[68]  Andrew R. Hall,et al.  Hepatic steatosis estimated microscopically versus digital image analysis , 2013, Liver international : official journal of the International Association for the Study of the Liver.

[69]  D. Jain,et al.  Cirrhosis Regression and Subclassification. , 2013, Surgical pathology clinics.

[70]  K. Sköld,et al.  Heat stabilization of blood spot samples for determination of metabolically unstable drug compounds. , 2013, Bioanalysis.

[71]  M. Murakami,et al.  Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression. , 2013, Journal of hepatology.

[72]  V. Paradis,et al.  Tumoral heterogeneity of hepatic cholangiocarcinomas revealed by MALDI imaging mass spectrometry , 2014, Proteomics.

[73]  R. Casadonte,et al.  Imaging mass spectrometry to discriminate breast from pancreatic cancer metastasis in formalin‐fixed paraffin‐embedded tissues , 2014, Proteomics.

[74]  Richard Torres,et al.  High-resolution, 2- and 3-dimensional imaging of uncut, unembedded tissue biopsy samples. , 2014, Archives of pathology & laboratory medicine.

[75]  S. Richter,et al.  Multi-centre evaluation of mass spectrometric identification of anaerobic bacteria using the VITEK® MS system. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[76]  T. Sakamoto,et al.  Detection of changes in the structure and distribution map of triacylglycerol in fatty liver model by MALDI-SpiralTOF , 2014, FEBS open bio.

[77]  K. Kim,et al.  Phosphatidylcholine Alteration Identified Using MALDI Imaging MS in HBV-Infected Mouse Livers and Virus-Mediated Regeneration Defects , 2014, PloS one.

[78]  K. Itoh,et al.  Label‐free visualization of acetaminophen‐induced liver injury by high‐speed stimulated Raman scattering spectral microscopy and multivariate image analysis , 2014, Pathology international.

[79]  P. Sakhuja Pathology of alcoholic liver disease, can it be differentiated from nonalcoholic steatohepatitis? , 2014, World journal of gastroenterology.

[80]  A. Burroughs,et al.  Collagen proportionate area is superior to other histological methods for sub-classifying cirrhosis and determining prognosis. , 2014, Journal of hepatology.

[81]  Xin Liu,et al.  Multiphoton microscopy in defining liver function , 2014, Journal of biomedical optics.

[82]  T. Arisawa,et al.  Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease. , 2014, World journal of gastroenterology.

[83]  A. Dohan,et al.  Transjugular liver biopsy: indications, technique and results. , 2014, Diagnostic and interventional imaging.

[84]  R. Zbinden,et al.  Evaluation of the Bruker MALDI Biotyper for Identification of Gram-Positive Rods: Development of a Diagnostic Algorithm for the Clinical Laboratory , 2014, Journal of Clinical Microbiology.

[85]  R. Wevers,et al.  Alpha-fetoprotein, a fascinating protein and biomarker in neurology. , 2014, European journal of paediatric neurology.

[86]  Farzad Fereidouni,et al.  Microscopy with UV Surface Excitation (MUSE) for slide-free histology and pathology imaging , 2015, Photonics West - Biomedical Optics.

[87]  Yue Zhu,et al.  Rapid and high-resolution imaging of human liver specimens by full-field optical coherence tomography , 2015, Journal of biomedical optics.

[88]  B. Nemes,et al.  Evaluation of Histological and non-Invasive Methods for the Detection of Liver Fibrosis: The Values of Histological and Digital Morphometric Analysis, Liver Stiffness Measurement and APRI Score , 2015, Pathology & Oncology Research.

[89]  Eoin Fahy,et al.  Biomarkers of NAFLD progression: a lipidomics approach to an epidemic1[S] , 2015, Journal of Lipid Research.

[90]  P. Gilligan,et al.  Cost Savings Realized by Implementation of Routine Microbiological Identification by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry , 2015, Journal of Clinical Microbiology.

[91]  U. Schubert,et al.  MALDI imaging-based classification of hepatocellular carcinoma and non-malignant lesions in fibrotic liver tissue , 2015, Zeitschrift für Gastroenterologie.

[92]  Xiaowen Liang,et al.  Real-time histology in liver disease using multiphoton microscopy with fluorescence lifetime imaging. , 2015, Biomedical optics express.

[93]  D. Amarapurkar,et al.  Indications of Liver Biopsy in the Era of Noninvasive Assessment of Liver Fibrosis. , 2015, Journal of clinical and experimental hepatology.

[94]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[95]  Robin Patel,et al.  MALDI-TOF MS for the diagnosis of infectious diseases. , 2015, Clinical chemistry.

[96]  Na Sun,et al.  High-mass-resolution MALDI mass spectrometry imaging of metabolites from formalin-fixed paraffin-embedded tissue , 2016, Nature Protocols.

[97]  Richard Torres,et al.  Multiphoton microscopy with clearing for three dimensional histology of kidney biopsies. , 2016, Biomedical optics express.

[98]  Abdelmoneim E. M. Kheir,et al.  Idiopathic neonatal hepatitis or extrahepatic biliary atresia? The role of liver biopsy. , 2016, Sudanese journal of paediatrics.

[99]  D. Newton,et al.  Cost Analysis of Implementing Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Plus Real-Time Antimicrobial Stewardship Intervention for Bloodstream Infections , 2016, Journal of Clinical Microbiology.

[100]  DeLiang Wang,et al.  A Deep Ensemble Learning Method for Monaural Speech Separation , 2016, IEEE/ACM Transactions on Audio, Speech, and Language Processing.

[101]  J. Nousbaum,et al.  Major changes in the number and indications of liver biopsy for chronic liver diseases over one decade in France , 2016, European journal of gastroenterology & hepatology.

[102]  K. Kharbanda,et al.  Treatment options for alcoholic and non-alcoholic fatty liver disease: A review , 2017, World journal of gastroenterology.

[103]  S. Davies,et al.  Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease , 2017, Hepatology.

[104]  Lawrence D. True,et al.  Light-sheet microscopy for slide-free non-destructive pathology of large clinical specimens , 2017, Nature Biomedical Engineering.

[105]  Kaikai Guo,et al.  Rapid focus map surveying for whole slide imaging with continues sample motion , 2017, Optics letters.

[106]  Y. Ucal,et al.  Clinical applications of MALDI imaging technologies in cancer and neurodegenerative diseases. , 2017, Biochimica et biophysica acta. Proteins and proteomics.

[107]  Hong You,et al.  New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment , 2017, Hepatology.

[108]  Andrew H. Beck,et al.  Diagnostic Assessment of Deep Learning Algorithms for Detection of Lymph Node Metastases in Women With Breast Cancer , 2017, JAMA.

[109]  Xiaowen Liang,et al.  Visualizing liver anatomy, physiology and pharmacology using multiphoton microscopy , 2017, Journal of biophotonics.

[110]  Hong Wang,et al.  An Inexpensive Digital Image Analysis Technique for Liver Fibrosis Quantification in Chronic Hepatitis B Patients. , 2017, Annals of hepatology.

[111]  Per E. Andrén,et al.  Yale School of Public Health Symposium on tissue imaging mass spectrometry: illuminating phenotypic heterogeneity and drug disposition at the molecular level , 2018, Human Genomics.

[112]  Gert B. Eijkel,et al.  Spatial Systems Lipidomics Reveals Nonalcoholic Fatty Liver Disease Heterogeneity , 2018, Analytical chemistry.

[113]  P. Bütikofer,et al.  Determination of the formation rate of phosphatidylethanol by phospholipase D (PLD) in blood and test of two selective PLD inhibitors. , 2018, Alcohol.

[114]  A. Wee,et al.  Progression and regression of fibrosis in viral hepatitis in the treatment era: the Beijing classification , 2018, Modern Pathology.

[115]  P. Hytiroglou,et al.  Regression of human cirrhosis: an update, 18 years after the pioneering article by Wanless et al. , 2018, Virchows Archiv.

[116]  L. N. Valenti,et al.  Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research , 2018, World journal of hepatology.

[117]  V. Cuccurullo,et al.  Microvascular Invasion in HCC: The Molecular Imaging Perspective , 2018, Contrast media & molecular imaging.

[118]  Qingming Luo,et al.  Optical clearing for multiscale biological tissues , 2018, Journal of biophotonics.

[119]  John A. Bowden,et al.  Examining heat treatment for stabilization of the lipidome. , 2018, Bioanalysis.

[120]  P. Chaurand,et al.  Mapping the triglyceride distribution in NAFLD human liver by MALDI imaging mass spectrometry reveals molecular differences in micro and macro steatosis , 2018, Analytical and Bioanalytical Chemistry.

[121]  Hanry Yu,et al.  Deep learning enables automated scoring of liver fibrosis stages , 2018, Scientific Reports.

[122]  Susana Comte-Walters,et al.  Mapping Extracellular Matrix Proteins in Formalin-Fixed, Paraffin-Embedded Tissues by MALDI Imaging Mass Spectrometry. , 2018, Journal of proteome research.

[123]  M. Arrese,et al.  The Evolving Role of Liver Biopsy in Non-alcoholic Fatty Liver Disease. , 2018, Annals of hepatology.

[124]  Chao-Ting Li,et al.  Inflammatory Cells Detection in H&E Staining Histology Images Using Deep Convolutional Neural Network with Distance Transformation , 2018, ICS.

[125]  Lydia P. Howell,et al.  Artificial Intelligence and Machine Learning in Pathology: The Present Landscape of Supervised Methods , 2019, Academic pathology.

[126]  P. Mistry,et al.  Exome Sequencing in Clinical Hepatology , 2019, Hepatology.

[127]  H. Guillou,et al.  Sphingolipid metabolism in non-alcoholic fatty liver diseases. , 2019, Biochimie.

[128]  D. Jain,et al.  Clinical utility of genomic analysis in adults with idiopathic liver disease. , 2019, Journal of hepatology.

[129]  Ming Ni,et al.  Automated classification of hepatocellular carcinoma differentiation using multiphoton microscopy and deep learning , 2019, Journal of biophotonics.

[130]  Chaoyang Zhang,et al.  Deep Learning Based Analysis of Histopathological Images of Breast Cancer , 2019, Front. Genet..

[131]  D. Jain,et al.  Organic Solute Transporter Alpha Deficiency: A Disorder With Cholestasis, Liver Fibrosis, and Congenital Diarrhea , 2019, Hepatology.

[132]  M. Fiel,et al.  Diagnosis of Liver Neoplasms by Computational and Statistical Image Analysis , 2019, Gastroenterology research.