{"id":"https://openalex.org/W2001537101","doi":"https://doi.org/10.1002/hep.23288","title":"One Step at a Time","display_name":"One Step at a Time","publication_year":2009,"publication_date":"2009-09-09","ids":{"openalex":"https://openalex.org/W2001537101","doi":"https://doi.org/10.1002/hep.23288","mag":"2001537101","pmid":"https://pubmed.ncbi.nlm.nih.gov/19787817"},"language":"en","primary_location":{"id":"doi:10.1002/hep.23288","doi":"https://doi.org/10.1002/hep.23288","is_oa":true,"landing_page_url":"https://doi.org/10.1002/hep.23288","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.23288","source":{"id":"https://openalex.org/S156174673","display_name":"Hepatology","issn_l":"0270-9139","issn":["0270-9139","1527-3350"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Hepatology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.23288","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5111692944","display_name":"Jayant A. Talwalkar","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1330342723","display_name":"Mayo Clinic","ror":"https://ror.org/02qp3tb03","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jayant A. Talwalkar","raw_affiliation_strings":["Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Center for Advanced Imaging Research, Mayo Clinic, Rochester, MN","fax: 507-284-0538"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Center for Advanced Imaging Research, Mayo Clinic, Rochester, MN","institution_ids":["https://openalex.org/I1330342723"]},{"raw_affiliation_string":"fax: 507-284-0538","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5111692944"],"corresponding_institution_ids":["https://openalex.org/I1330342723"],"apc_list":{"value":2900,"currency":"USD","value_usd":2900},"apc_paid":null,"fwci":0.4477,"has_fulltext":true,"cited_by_count":4,"citation_normalized_percentile":{"value":0.70552642,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":94},"biblio":{"volume":"50","issue":"4","first_page":"1000","last_page":"1003"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10351","display_name":"Liver Disease Diagnosis and Treatment","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2713","display_name":"Epidemiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10351","display_name":"Liver Disease Diagnosis and Treatment","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2713","display_name":"Epidemiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11834","display_name":"Liver Diseases and Immunity","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10966","display_name":"Liver physiology and pathology","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/non-alcoholic-steatohepatitis","display_name":"nonalcoholic steatohepatitis","score":0.9789999723434448},{"id":"https://openalex.org/keywords/non-alcoholic-fatty-liver-disease","display_name":"non-alcoholic fatty liver disease","score":0.9470000267028809},{"id":"https://openalex.org/keywords/cytokeratin-18","display_name":"cytokeratin 18","score":0.8809999823570251},{"id":"https://openalex.org/keywords/plasma-biomarkers","display_name":"plasma biomarkers","score":0.7900000214576721},{"id":"https://openalex.org/keywords/nash-diagnosis","display_name":"NASH diagnosis","score":0.7120000123977661},{"id":"https://openalex.org/keywords/hepatocyte-apoptosis","display_name":"hepatocyte apoptosis","score":0.7329999804496765},{"id":"https://openalex.org/keywords/liver-fibrosis","display_name":"liver fibrosis","score":0.5619999766349792},{"id":"https://openalex.org/keywords/non-invasive-diagnosis","display_name":"non-invasive diagnosis","score":0.7509999871253967},{"id":"https://openalex.org/keywords/liver-biopsy-histopathology","display_name":"liver biopsy histology","score":0.5699999928474426},{"id":"https://openalex.org/keywords/diagnostic-accuracy","display_name":"diagnostic accuracy","score":0.4300000071525574}],"concepts":[{"id":"https://openalex.org/C2776954865","wikidata":"https://www.wikidata.org/wiki/Q1546498","display_name":"Nonalcoholic fatty liver disease","level":4,"score":0.7679803967475891},{"id":"https://openalex.org/C2777766500","wikidata":"https://www.wikidata.org/wiki/Q360841","display_name":"Liver biopsy","level":3,"score":0.6809735298156738},{"id":"https://openalex.org/C41260117","wikidata":"https://www.wikidata.org/wiki/Q668064","display_name":"Hepatology","level":2,"score":0.654391884803772},{"id":"https://openalex.org/C2779478299","wikidata":"https://www.wikidata.org/wiki/Q2335423","display_name":"Steatohepatitis","level":4,"score":0.6178229451179504},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.616733193397522},{"id":"https://openalex.org/C2777214474","wikidata":"https://www.wikidata.org/wiki/Q147778","display_name":"Cirrhosis","level":2,"score":0.6067069172859192},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5574470162391663},{"id":"https://openalex.org/C2778772119","wikidata":"https://www.wikidata.org/wiki/Q6058862","display_name":"Fatty liver","level":3,"score":0.5433242917060852},{"id":"https://openalex.org/C90924648","wikidata":"https://www.wikidata.org/wiki/Q120569","display_name":"Gastroenterology","level":1,"score":0.4871065616607666},{"id":"https://openalex.org/C2777075537","wikidata":"https://www.wikidata.org/wiki/Q929737","display_name":"Liver disease","level":2,"score":0.4860968589782715},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.43579670786857605},{"id":"https://openalex.org/C3018708256","wikidata":"https://www.wikidata.org/wiki/Q1546498","display_name":"Nonalcoholic steatohepatitis","level":5,"score":0.4128724932670593},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.358961820602417},{"id":"https://openalex.org/C2775934546","wikidata":"https://www.wikidata.org/wiki/Q179991","display_name":"Biopsy","level":2,"score":0.35341036319732666},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.32313019037246704},{"id":"https://openalex.org/C99454951","wikidata":"https://www.wikidata.org/wiki/Q932068","display_name":"Environmental health","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D001706","descriptor_name":"Biopsy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000175","qualifier_name":"diagnosis","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D011237","descriptor_name":"Predictive Value of Tests","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012680","descriptor_name":"Sensitivity and Specificity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015415","descriptor_name":"Biomarkers","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":false},{"descriptor_ui":"D053538","descriptor_name":"Keratin-18","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1002/hep.23288","doi":"https://doi.org/10.1002/hep.23288","is_oa":true,"landing_page_url":"https://doi.org/10.1002/hep.23288","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.23288","source":{"id":"https://openalex.org/S156174673","display_name":"Hepatology","issn_l":"0270-9139","issn":["0270-9139","1527-3350"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Hepatology","raw_type":"journal-article"},{"id":"pmid:19787817","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/19787817","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Hepatology (Baltimore, Md.)","raw_type":"Comment"}],"best_oa_location":{"id":"doi:10.1002/hep.23288","doi":"https://doi.org/10.1002/hep.23288","is_oa":true,"landing_page_url":"https://doi.org/10.1002/hep.23288","pdf_url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.23288","source":{"id":"https://openalex.org/S156174673","display_name":"Hepatology","issn_l":"0270-9139","issn":["0270-9139","1527-3350"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Hepatology","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.98580002784729,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2001537101.pdf","grobid_xml":"https://content.openalex.org/works/W2001537101.grobid-xml"},"referenced_works_count":22,"referenced_works":["https://openalex.org/W91108901","https://openalex.org/W1969770795","https://openalex.org/W1978036176","https://openalex.org/W1985365374","https://openalex.org/W1986639152","https://openalex.org/W1988826453","https://openalex.org/W2001837599","https://openalex.org/W2009135063","https://openalex.org/W2023075325","https://openalex.org/W2027557878","https://openalex.org/W2034188379","https://openalex.org/W2046475112","https://openalex.org/W2060847352","https://openalex.org/W2094419740","https://openalex.org/W2112496618","https://openalex.org/W2124858725","https://openalex.org/W2151769300","https://openalex.org/W2156792510","https://openalex.org/W2157162247","https://openalex.org/W2157636987","https://openalex.org/W2163803773","https://openalex.org/W2168898273"],"related_works":["https://openalex.org/W2505200144","https://openalex.org/W2060847352","https://openalex.org/W7097634296","https://openalex.org/W2073222975","https://openalex.org/W4322492022","https://openalex.org/W4294489206","https://openalex.org/W1973645169","https://openalex.org/W1981623819","https://openalex.org/W2470218709","https://openalex.org/W2168898273"],"abstract_inverted_index":{"In":[0,226,408,672,919],"addition":[1],"to":[2,6,39,59,176,186,211,403,567,632,646,688,744,767,828,866,954,1020,1070,1120,1149,1177,1192,1210,1267,1338,1350,1386,1393,1401,1408,1447,1466,1495,1504,1560,1634],"work":[3,1099,1524],"being":[4,166,200],"done":[5],"characterize":[7],"the":[8,23,43,60,114,128,153,196,204,240,312,345,350,366,372,404,410,431,483,491,526,535,546,554,571,593,604,616,634,690,712,772,790,819,847,875,897,911,926,929,941,958,968,998,1047,1078,1085,1113,1121,1132,1136,1138,1142,1166,1179,1207,1222,1237,1261,1356,1362,1406,1464,1471,1480,1536,1564,1569,1579,1603,1613,1623,1635,1639],"geoepidemiology":[9],"of":[10,25,34,45,77,156,198,206,229,242,305,315,344,374,428,445,466,485,514,521,528,537,548,556,573,585,595,618,637,651,655,667,678,730,774,785,821,850,914,957,980,1000,1025,1050,1082,1087,1115,1128,1183,1196,1217,1224,1255,1263,1274,1345,1358,1374,1488,1566,1582,1617],"nonalcoholic":[11,65,100,105],"fatty":[12,101,217,258],"liver":[13,27,61,90,102,135,181,218,259,346,561,624,715,1002,1095,1156,1339],"disease":[14,86,731,881,1157],"(NAFLD),1":[15],"there":[16,49,137,762,1227],"have":[17,582,1228,1250,1277,1328,1463],"been":[18,125,583,1230,1441],"equally":[19],"important":[20,71,191,1075],"discoveries":[21],"surrounding":[22],"pathogenesis":[24,547],"this":[26,46,75,157,227,264,515,670,786,839,920,1051,1197,1437,1468],"disease.":[28,1360],"At":[29],"one":[30,922],"time,":[31],"a":[32,207,237,249,292,337,384,425,488,495,522,538,576,674,722,753,807,878,891,915,1088,1110,1116,1129,1382],"condition":[33,879],"\"two":[35],"hits\"":[36],"was":[37,266,329,379,452,661,935,1175],"thought":[38],"be":[40,221,610,682,707,742,780,800,804,842,994,1015,1586,1632],"necessary":[41,1209],"for":[42,83,117,159,170,263,296,331,391,472,482,503,601,692,718,782,809,835,873,932,947,1008,1053,1091,1152,1189,1204,1239,1248,1308,1491,1508,1555,1588,1599,1612,1638],"origin":[44],"disease,":[47],"but":[48,189,1203,1522],"is":[50,79,183,278,826,882,1206,1426,1525,1540,1609],"now":[51,1205],"evidence":[52],"pointing":[53],"toward":[54,1519],"several":[55,764,1231],"additional":[56,783,1098,1523],"mechanisms":[57,1254],"contributing":[58],"injury":[62,376],"known":[63],"as":[64,175,248,401,752,806,885,1016,1029,1031,1059,1381,1427,1430,1547,1592],"steatohepatitis":[66],"(NASH).2":[67],"NASH":[68,215,254,319,335,419,423,440,505,660,1092,1153,1414],"remains":[69,113,1200,1367],"an":[70,442,479,868,1073,1506,1548],"phenotypic":[72],"state,":[73],"because":[74],"subgroup":[76],"patients":[78,119,213,252,417,1055,1432,1497,1559,1596],"deemed":[80],"at":[81,589,938,984],"high-risk":[82],"developing":[84],"progressive":[85],"resulting":[87,1037],"in":[88,281,298,362,397,416,545,563,615,640,663,685,704,727,769,792,813,890,909,1010,1045,1077,1163,1236,1312,1332,1354,1369,1444,1451,1470,1510,1535,1558,1602],"cirrhosis,":[89],"failure":[91],"requiring":[92],"transplantation,":[93],"or":[94,424,441,560,880,1299,1347,1562,1573,1615],"death.3":[95],"CK-18,":[96],"cytokeratin":[97,244],"18;":[98],"NAFLD,":[99,203,569,619],"disease;":[103],"NASH,":[104,171,532],"steatohepatitis;":[106],"ROC,":[107],"receiver":[108,959],"operating":[109,960],"characteristic.":[110],"Liver":[111],"histology":[112,625],"gold":[115,1383],"standard":[116,1384],"identifying":[118,504,836,1054],"with":[120,134,180,202,214,253,257,286,308,334,399,418,439,531,659,721,757,893,1056,1165,1296,1315,1411,1422,1433,1498,1597],"NASH.":[121,429,446,486,642,1567],"Although":[122,1246,1436],"much":[123],"has":[124,1439],"said":[126],"about":[127],"sampling":[129,638,702,746],"error":[130,703],"and":[131,145,168,224,284,323,360,460,464,499,533,603,620,628,796,903,944,976,1004,1034,1061,1080,1141,1154,1168,1181,1259,1320,1325,1371,1377,1417,1477,1484],"observer":[132],"variation":[133,791],"biopsy,4":[136],"are":[138,165,649,763,907,1068],"also":[139,453,700,741,1041,1251,1303,1502],"concerns":[140],"regarding":[141,789],"increased":[142],"resource":[143],"utilization":[144],"reduced":[146],"patient":[147,833,892,1032],"acceptance":[148],"which":[149,542,579,859,1395,1552],"will":[150,173,725,779,799,841,1013,1040,1533,1545,1575,1585],"further":[151,1043],"limit":[152],"population-wide":[154],"use":[155,520,1509],"test":[158,210,696,972,1103,1397,1551],"detecting":[160,299,1240,1309,1333,1431],"NASH.5":[161],"Because":[162],"effective":[163],"therapies":[164,1517],"developed":[167],"tested":[169],"questions":[172],"remain":[174],"whether":[177],"fibrosis":[178,1243,1270,1311,1335],"assessment":[179],"biopsy":[182,347,716],"sensitive":[184],"enough":[185],"detect":[187],"small":[188],"potentially":[190],"changes":[192],"over":[193,794,1282],"time.":[194],"Given":[195],"preponderance":[197],"individuals":[199,530,720,1009,1410],"identified":[201],"recognition":[205],"noninvasive,":[208],"versatile":[209],"discriminate":[212],"from":[216,236,255,349,377,383,575,1038,1244,1364,1420],"alone":[219,717,1425],"would":[220,681,1158,1501],"highly":[222,683],"practical":[223],"useful.":[225],"issue":[228],"HEPATOLOGY,":[230],"Feldstein":[231,1476],"et":[232],"al.6":[233],"present":[234,280,883],"results":[235,388,992],"study":[238,265,302,516,536,647,1044,1474],"examining":[239,1515],"role":[241,295,751,1076],"plasma":[243,457,476,734,775,949,1489],"18":[245],"(CK-18)":[246],"fragments":[247,493,736,934],"biomarker":[250,808,1090,1117,1130,1190,1225],"distinguishing":[251],"those":[256,421,1421],"alone.":[260],"The":[261,301,387,512,653,1023,1194,1607],"rationale":[262],"based":[267,506],"on":[268,507,597,623,695,1072,1253,1578],"emerging":[269,1449],"data":[270,596,622,1265,1363,1450],"suggesting":[271],"that":[272,606,857,877,925,970,1458,1541],"hepatocyte":[273,738],"cell":[274,888],"death":[275],"by":[276,381,612,711,1186,1475,1622],"apoptosis":[277,540,739],"typically":[279],"animal":[282,1452],"models":[283,1453],"humans":[285],"NASH,7":[287],"including":[288],"preliminary":[289,1455],"studies":[290,559,687,1366,1392,1446],"implying":[291],"potential":[293,473,586,635,691,745,912,1465,1485],"diagnostic":[294,489,509,754,760,848,987,1102,1233,1280,1306,1571],"CK-18":[297,328,356,394,432,458,477,492,607,735,776,803,823,851,933,950,1006,1490,1542],"NASH.8-10":[300],"population":[303],"consisted":[304],"139":[306],"subjects":[307,398,438,566,668,1314],"biopsy-proven":[309],"NAFLD":[310,378,400,705,1249,1598],"representing":[311,737],"National":[313],"Institutes":[314],"Health":[316],"(NIH)":[317],"sponsored":[318],"Clinical":[320,853],"Research":[321],"Network":[322],"150":[324,405],"age-matched":[325],"controls.":[326],"Plasma":[327,355],"measured":[330],"each":[332],"subject":[333,743],"using":[336,365],"blood":[338,352,887],"sample":[339],"taken":[340],"within":[341,669,1161],"3":[342],"months":[343],"obtained":[348],"NIH":[351],"bank":[353],"repository.":[354],"measurements":[357],"were":[358,389,413],"collected":[359],"processed":[361],"different":[363],"centers":[364,798],"same":[367],"enzyme-linked":[368],"immunosorbent":[369],"assay,":[370],"while":[371,1126],"type":[373],"histological":[375,461,656,679],"verified":[380],"review":[382],"single":[385,577,1283],"hepatopathologist.":[386],"noted":[390,454],"significantly":[392,414],"higher":[393,415],"fragment":[395,777,824,951,1543],"levels":[396,433,952,1007,1544],"compared":[402,1019,1337],"healthy":[406,564],"volunteers.":[407],"addition,":[409],"average":[411],"values":[412,459,608,778,825,862,1327,1344],"versus":[420],"without":[422],"borderline":[426],"diagnosis":[427,444,1079],"However,":[430,733,1058,1361],"could":[434,609,982],"not":[435,581,1014,1440,1610],"distinguish":[436,1409],"between":[437,455,497,501,797,832,974,1390],"indeterminate":[443],"A":[447],"modest":[448],"yet":[449],"positive":[450,900],"association":[451],"mean":[456,822],"activity":[462],"score":[463],"stage":[465,1413],"hepatic":[467],"fibrosis.":[468,1435],"Finally,":[469,1084],"after":[470],"adjusting":[471],"confounding":[474],"variables,":[475],"remained":[478],"independent":[480,1107,1290],"predictor":[481],"presence":[484,1357,1565],"As":[487,709,756],"test,":[490],"retained":[494],"sensitivity":[496,942,1324],"65%\u201377%":[498],"specificity":[500,945,1326],"65%\u201392%":[502],"various":[508],"threshold":[510,870,988],"values.":[511,989],"advantages":[513],"include":[517,552],"(1)":[518,553],"its":[519,750],"multicenter":[523,815],"approach,":[524,1198],"(2)":[525,570],"availability":[527,1487],"well-characterized":[529],"(3)":[534,592],"plasma-based":[539],"marker":[541,1284],"appears":[543],"relevant":[544,837,1429],"NAFLD.":[549,1083,1316,1499],"Potential":[550],"limitations":[551],"absence":[555,594,617],"reported":[557],"imaging":[558,1295,1322],"biopsies":[562],"control":[565],"exclude":[568],"selection":[572],"controls":[574,587,602],"center":[578],"may":[580,740,1462],"representative":[584],"selected":[588],"other":[590,765,1062,1155],"centers,":[591],"body":[598],"mass":[599],"index":[600],"possibility":[605,969,1539],"influenced":[611],"obesity/insulin":[613],"resistance":[614],"(4)":[621],"specimen":[626],"size":[627],"portal":[629],"tract":[630],"number":[631],"determine":[633,1394],"effect":[636,812],"variability":[639,747],"recognizing":[641],"Several":[643],"points":[644],"related":[645],"design":[648],"worthy":[650],"discussion.":[652],"frequency":[654],"findings":[657,680],"consistent":[658],"observed":[662],"more":[664,675,1065],"than":[665,1628],"50%":[666],"study.":[671],"turn,":[673],"even":[676,1286],"distribution":[677],"desirable":[684],"future":[686],"minimize":[689],"spectrum":[693,1375],"bias":[694,1376],"performance":[697,849,913,1104,1281],"results.":[698],"We":[699],"know":[701,1530],"can":[706,923,1529],"significant.":[708],"stated":[710],"authors,":[713],"utilizing":[714],"risk-stratifying":[719],"common":[723],"disorder":[724],"result":[726],"unwanted":[728],"misclassification":[729,1027],"stage.":[732],"when":[748,845,1018,1287,1336],"assessing":[749,810,846,874],"test.":[755,787,918],"all":[758],"new":[759],"tests,":[761,1323],"caveats":[766],"keep":[768],"mind.":[770],"Understanding":[771],"reproducibility":[773],"required":[781,1526],"investigations":[784,1273],"Knowledge":[788],"measurement":[793],"time":[795],"critical,":[801],"should":[802,1398,1631],"used":[805],"therapeutic":[811,1600],"subsequent,":[814],"clinical":[816,1011,1048,1143,1215,1402,1512],"trials.":[817,1404],"Whereas":[818],"calculation":[820],"helpful":[827,844],"perform":[829,1534],"statistical":[830],"tests":[831,858],"subgroups":[834],"differences,":[838],"approach":[840,1052,1572],"less":[843],"fragments.":[852],"experience":[854],"tells":[855],"us":[856,865],"provide":[860,1505],"continuous":[861],"still":[863],"require":[864,1042,1159],"identify":[867],"optimal":[869,955,1570],"(or":[871,1093],"cutoff)":[872],"likelihood":[876],"(such":[884],"white":[886],"count":[889],"suspected":[894],"appendicitis).":[895],"Assessing":[896],"sensitivity,":[898],"specificity,":[899],"predictive":[901,905,916,1343],"value,":[902],"negative":[904,978,1342],"value":[906,931],"valuable":[908],"understanding":[910],"laboratory":[917],"study,":[921],"observe":[924],"area":[927],"under":[928,1124],"curve":[930],"considered":[936,995],"excellent":[937,1305],"0.83.":[939],"Subsequently,":[940],"(71%\u201375%)":[943],"(81%\u201385%)":[946],"certain":[948],"correspond":[953],"areas":[956],"characteristic":[961],"(ROC)":[962],"curve.":[963],"These":[964],"results,":[965],"however,":[966,1199],"suggest":[967],"false-positive":[971],"rates":[973,979],"25%\u201329%":[975],"false":[977],"15%\u201319%":[981],"occur":[983],"these":[985,991,1026,1060,1365,1391,1583],"corresponding":[986,1636],"Furthermore,":[990,1405],"might":[993],"ideal":[996],"since":[997],"procurement":[999],"satisfactory":[1001],"specimens":[1003],"measurable":[1005],"practice":[1012],"complete":[1017],"experimental":[1021],"settings.":[1022],"impact":[1024],"rates,":[1028],"well":[1030],"preference":[1033],"long-term":[1035],"outcomes":[1036],"testing,":[1039],"determining":[1046,1589],"effectiveness":[1049,1403,1581],"NASH.11":[1057],"biomarkers":[1063,1151,1213,1247],"become":[1064],"sophisticated,":[1066],"they":[1067],"likely":[1069],"take":[1071],"increasingly":[1074],"management":[1081],"validation":[1086,1114],"noninvasive":[1089,1396,1445],"any":[1094,1618],"disease)":[1096],"requires":[1097],"beyond":[1100],"verifying":[1101],"characteristics":[1105],"among":[1106,1289],"populations.":[1108],"From":[1109],"regulatory":[1111],"perspective,":[1112],"usually":[1118],"refers":[1119],"assay":[1122],"method":[1123],"investigation,":[1125],"qualification":[1127],"defines":[1131,1553],"evidentiary":[1133],"process":[1134,1140,1174],"connecting":[1135],"biomarker,":[1137],"biological":[1139,1482],"end":[1144],"point":[1145],"together.12":[1146],"Organizing":[1147],"efforts":[1148],"\"qualify\"":[1150],"collaboration":[1160],"consortia":[1162],"cooperation":[1164],"Food":[1167],"Drug":[1169],"Administration.":[1170],"This":[1171,1473],"formalized,":[1172],"central":[1173],"designed":[1176],"overcome":[1178],"complexity":[1180],"lack":[1182],"direction":[1184],"provided":[1185],"unstructured":[1187],"processes":[1188],"approval":[1191],"date.13":[1193],"viability":[1195],"somewhat":[1201],"uncertain":[1202],"pathway":[1208],"incorporate":[1211],"desired":[1212],"into":[1214],"trials":[1216],"novel":[1218,1516],"drug":[1219],"therapies.14":[1220],"Despite":[1221],"complexities":[1223],"validation,":[1226],"already":[1229],"non-invasive":[1232],"indices":[1234,1285],"presented":[1235],"literature":[1238],"clinically":[1241,1428],"significant":[1242],"NAFLD.15":[1245],"focused":[1252],"oxidative":[1256],"stress,":[1257],"inflammation,":[1258],"apoptosis,":[1260,1521],"majority":[1262],"recent":[1264],"continues":[1266],"revolve":[1268],"around":[1269],"detection.":[1271],"Recent":[1272],"multivariable":[1275],"panels":[1276],"demonstrated":[1278],"improved":[1279],"studied":[1288],"populations.16-19":[1291],"(Table":[1292],"1).":[1293],"Elastography":[1294],"transient":[1297],"ultrasound20":[1298],"magnetic":[1300,1459],"resonance21":[1301],"platforms":[1302],"provides":[1304],"accuracy":[1307,1380],"advanced":[1310,1334,1359,1434],"human":[1313,1456],"For":[1317],"both":[1318],"serum":[1319],"elastography":[1321,1461],"exceeded":[1329],"80%,":[1330],"respectively,":[1331],"biopsy.":[1340],"Additionally,":[1341],"95%":[1346],"greater":[1348],"help":[1349],"improve":[1351],"our":[1352,1493,1595],"confidence":[1353],"excluding":[1355],"cross-sectional":[1368],"nature,":[1370],"persistent":[1372],"issues":[1373],"variable":[1378],"histologic":[1379],"continue":[1385],"prevent":[1387],"direct":[1388],"comparisons":[1389],"move":[1399],"forward":[1400],"ability":[1407,1494],"early":[1412],"(i.e.,":[1415],"inflammation":[1416],"no":[1418],"fibrosis)":[1419],"simple":[1423],"steatosis":[1424],"scenario":[1438],"often":[1442],"addressed":[1443],"date,":[1448],"verifies":[1454],"experiences21":[1457],"resonance":[1460],"serve":[1467],"purpose":[1469],"future.22":[1472],"colleagues":[1478],"demonstrates":[1479],"simplicity,":[1481],"plausibility,":[1483],"widespread":[1486],"improving":[1492],"risk-stratify":[1496,1594],"It":[1500],"appear":[1503],"advantage":[1507],"proof-of-concept":[1511],"trial":[1513],"settings":[1514],"geared":[1518],"inhibiting":[1520],"before":[1527],"we":[1528,1591],"how":[1531,1590],"it":[1532],"clinic.":[1537],"One":[1538],"function":[1546],"\"added":[1549],"value\"":[1550],"algorithms":[1554],"subsequent":[1556],"testing":[1557],"confirm":[1561],"deny":[1563],"Whatever":[1568],"approaches":[1574],"be,":[1576],"information":[1577,1620],"comparative":[1580],"strategies":[1584],"crucial":[1587],"clinicians":[1593],"interventions":[1601],"future.":[1604],"Please":[1605],"note:":[1606],"publisher":[1608],"responsible":[1611],"content":[1614],"functionality":[1616],"supporting":[1619],"supplied":[1621],"authors.":[1624],"Any":[1625],"queries":[1626],"(other":[1627],"missing":[1629],"content)":[1630],"directed":[1633],"author":[1637],"article.":[1640]},"counts_by_year":[{"year":2017,"cited_by_count":1},{"year":2013,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}