2024
Clinicopathologic features and prognosis of steatohepatitic hepatocellular carcinoma based on varying cutoffs of tumoral steatohepatitic changes
Zhang T, Niu N, Taddei T, Jain D, Zhang X. Clinicopathologic features and prognosis of steatohepatitic hepatocellular carcinoma based on varying cutoffs of tumoral steatohepatitic changes. American Journal Of Clinical Pathology 2024, aqae136. PMID: 39418121, DOI: 10.1093/ajcp/aqae136.Peer-Reviewed Original ResearchSH-HCCSteatohepatitic hepatocellular carcinomaHepatocellular carcinomaLiver diseaseHepatitis C virus infectionC virus infectionStage of fibrosisPresence of steatohepatitisOverall survivalHistological subtypesPrognostic factorsHCC subtypesBackground liverHCC casesClinicopathological featuresConventional HCCHistopathological patternsHyaline globulesTumor cellsMallory-Denk bodiesGlycogenated nucleiSteatotic liver diseaseHCCSurvival analysisSteatohepatitisvon Meyenburg complexes are more frequently associated with cholangiocarcinoma
Jain D, Khandakar B, Ni P, Kenney B, Qin L, Deshpande V, Fiel M. von Meyenburg complexes are more frequently associated with cholangiocarcinoma. Journal Of Clinical Pathology 2024, jcp-2024-209572. PMID: 38729770, DOI: 10.1136/jcp-2024-209572.Peer-Reviewed Original ResearchVon Meyenburg complexesHilar CCHepatic resectionCC casesChronic viral hepatitis BAssociated liver disordersMeyenburg complexesProgress to cholangiocarcinomaDysplasia/carcinoma in situMetastatic colon carcinomaViral hepatitis BCases of CCBile duct adenomaPolycystic kidney diseaseAssociated with cholangiocarcinomaBenign lesionsCryptogenic cirrhosisHepatitis BBiliary diseaseColon carcinomaMiscellaneous disordersKidney diseaseLiver diseaseCholangiocarcinomaLiver disordersAcute Hepatitis due to Primary Human Immunodeficiency Virus Infection
Elliott E, Smith D, Lipscomb J, Banini B, Meurer L, Vanderford T, Johnson J, Jain D, Achhra A. Acute Hepatitis due to Primary Human Immunodeficiency Virus Infection. Open Forum Infectious Diseases 2024, 11: ofae170. PMID: 38585186, PMCID: PMC10996125, DOI: 10.1093/ofid/ofae170.Peer-Reviewed Original ResearchHuman immunodeficiency virusHuman immunodeficiency virus infectionAcute hepatitisPrimary human immunodeficiency virus infectionConsistent with acute hepatitisPrimary human immunodeficiency virusHuman immunodeficiency virus p24 antigenAcute retroviral syndromeImmunodeficiency virus infectionSevere acute hepatitisHIV proviral DNAAcute liver diseaseP24 antigenImmunodeficiency virusLaboratory abnormalitiesSystemic manifestationsRare caseLiver diseaseProviral DNAVirus infectionLiver histopathologyHepatitisCell compartmentParenchymal cellsLiver tissue
2023
Diagnosis and classification of vascular liver disorders
González I, Jain D. Diagnosis and classification of vascular liver disorders. Diagnostic Histopathology 2023, 29: 36-51. DOI: 10.1016/j.mpdhp.2022.10.005.Peer-Reviewed Original ResearchLiver vasculatureVascular liver disordersUnderlying liver diseaseNoncirrhotic portal hypertensionAcute liver failureDual blood supplyDiverse clinical presentationsTerminal portal venulesKey histologicPortal hypertensionAtypical presentationLiver biopsyLiver failureClinical featuresClinical presentationHepatic arteryLiver diseaseUnclear diagnosisHepatic veinHistologic findingsPortal veinChallenging disorderLiver disordersBlood supplyHepatic sinusoids
2022
An update on ductal plate malformations and fibropolycystic diseases of the liver
Mirza H, Besse W, Somlo S, Weinreb J, Kenney B, Jain D. An update on ductal plate malformations and fibropolycystic diseases of the liver. Human Pathology 2022, 132: 102-113. PMID: 35777701, DOI: 10.1016/j.humpath.2022.06.022.Peer-Reviewed Original ResearchConceptsDuctal plate malformationLiver diseaseAdult polycystic liver diseaseAutosomal dominant polycystic kidneyFibropolycystic liver diseaseIsolated liver involvementCongenital hepatic fibrosisPolycystic liver diseaseVon Meyenburg complexesGenetic underpinningsMultiple clinical phenotypesFibropolycystic diseasePortal hypertensionCaroli's diseaseLiver involvementLiver cystsMeyenburg complexesHepatic fibrosisFibrocystic lesionsHepatocellular malignanciesCyst enlargementAbnormal organ developmentPolycystic kidneysAnimal modelsHepatocellular malignancyThe many faces and pathologic diagnostic challenges of autoimmune hepatitis
Zhang X, Jain D. The many faces and pathologic diagnostic challenges of autoimmune hepatitis. Human Pathology 2022, 132: 114-125. PMID: 35753409, DOI: 10.1016/j.humpath.2022.06.019.Peer-Reviewed Original ResearchConceptsAutoimmune hepatitisHistological featuresLiver diseaseAcute-onset autoimmune hepatitisDiagnosis of AIHEnd-stage liver diseaseChronic inflammatory liver diseasePathologic diagnostic challengeFatal liver failureInflammatory liver diseaseTypical histological featuresCareful clinicopathological correlationRoutine clinical practiceMajor differential diagnosisImmunosuppressive treatmentLiver histologySpecific autoantibodiesLiver failurePrompt diagnosisHistological presentationClinicopathological correlationInternational Working GroupPathological featuresDiagnostic challengeHistopathologic spectrumConsensus recommendations for histological criteria of autoimmune hepatitis from the International AIH Pathology Group
Lohse AW, Sebode M, Bhathal PS, Clouston AD, Dienes HP, Jain D, Gouw ASH, Guindi M, Kakar S, Kleiner DE, Krech T, Lackner C, Longerich T, Saxena R, Terracciano L, Washington K, Weidemann S, Hübscher SG, Tiniakos D. Consensus recommendations for histological criteria of autoimmune hepatitis from the International AIH Pathology Group. Liver International 2022, 42: 1058-1069. PMID: 35230735, DOI: 10.1111/liv.15217.Peer-Reviewed Original ResearchConceptsAutoimmune hepatitisChronic autoimmune hepatitisLobular hepatitisLymphoplasmacytic hepatitisInflammatory changesLiver diseaseHistological featuresHistological criteriaConsensus criteriaInternational consensus criteriaExpert liver pathologistsDelphi panel approachChronic presentationAcute presentationLiver biopsyHistological diagnosisHistopathological diagnosisLiver pathologistsLiver pathologyConsensus statementConsensus recommendationsHepatitisPathology groupDisease severityPeriportal regionTCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut‐liver crosstalk
Bhat N, Esteghamat F, Chaube BK, Gunawardhana K, Mani M, Thames C, Jain D, Ginsberg HN, Fernandes‐Hernando C, Mani A. TCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut‐liver crosstalk. The FASEB Journal 2022, 36: e22185. PMID: 35133032, PMCID: PMC9624374, DOI: 10.1096/fj.202101607r.Peer-Reviewed Original ResearchConceptsGut-liver crosstalkBile synthesisDiet-induced fatty liver diseaseSmall intestineHepatic bile saltIntestinal lipid uptakePlasma bile saltsFatty liver diseaseTreatment of NASHColorectal cancer cellsBile saltsConditional knockout modelHuman NASHFatty liverLiver diseaseFXR activationClinical trialsEnterohepatic circulationTranscription factor TCF4Fl/Hepatic levelsBile acidsEndocrine regulatorLipid uptakeIntestinal epitheliumDyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice
Bhat N, Narayanan A, Fathzadeh M, Kahn M, Zhang D, Goedeke L, Neogi A, Cardone RL, Kibbey RG, Fernandez-Hernando C, Ginsberg HN, Jain D, Shulman G, Mani A. Dyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice. Journal Of Clinical Investigation 2022, 132: e153724. PMID: 34855620, PMCID: PMC8803348, DOI: 10.1172/jci153724.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisNonalcoholic steatohepatitisInsulin resistanceHepatic lipogenesisElevated de novo lipogenesisNonalcoholic fatty liver diseaseFatty liver diseaseLiver of patientsHepatic glycogen storageHigh-sucrose dietHepatic insulin resistanceFatty acid uptakeMetabolic syndromeLiver diseaseHepatic steatosisTriacylglycerol secretionNovo lipogenesisHepatic insulinTherapeutic targetImpaired activationAcid uptakeGlycogen storageMouse liverLiverLipogenesis
2021
Hepatocellular Carcinoma
Jain A, Mazer B, Deng Y, Ciarleglio M, Jain D, Taddei T, Zhang X. Hepatocellular Carcinoma. American Journal Of Clinical Pathology 2021, 157: 305-313. PMID: 34542582, DOI: 10.1093/ajcp/aqab125.Peer-Reviewed Original ResearchConceptsAnaplastic tumor cellsHepatocellular carcinomaNoncirrhotic liverVascular invasionHistologic patternCirrhotic liverTumor cellsClear cell subtypePathogenesis of HCCHigh histologic gradeLarger tumor sizeHigher tumor stageHigh tumor gradeHigh rateHepatitis BHepatitis CLiver diseaseTumor sizeHistologic gradeTumor stageTumor gradePathologic differencesHCC casesRetrospective analysisPathology archivesGIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension
Drzewiecki K, Choi J, Brancale J, Leney-Greene MA, Sari S, Dalgiç B, Aksu A, Şahin G, Ozen A, Baris S, Karakoc-Aydiner E, Jain D, Kleiner D, Schmalz M, Radhakrishnan K, Zhang J, Hoebe K, Su HC, Pereira JP, Lenardo MJ, Lifton RP, Vilarinho S. GIMAP5 maintains liver endothelial cell homeostasis and prevents portal hypertension. Journal Of Experimental Medicine 2021, 218: e20201745. PMID: 33956074, PMCID: PMC8105721, DOI: 10.1084/jem.20201745.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsPortal hypertensionEndothelial cell homeostasisHepatic endothelial cellsEndothelial cellsLiver diseaseUnexplained portal hypertensionGlobal health problemSinusoidal endothelial cellsCell homeostasisSingle-cell RNA-sequencing analysisHypertensionMouse modelHealth problemsMice resultsGimap5RNA sequence analysisMajor contributorCritical regulatorDiseaseCellsDamaging mutationsHomeostasisDecompensationMorbidityEvolution of the liver biopsy and its future
Jain D, Torres R, Celli R, Koelmel J, Charkoftaki G, Vasiliou V. Evolution of the liver biopsy and its future. Translational Gastroenterology And Hepatology 2021, 6: 20-20. PMID: 33824924, PMCID: PMC7829074, DOI: 10.21037/tgh.2020.04.01.Peer-Reviewed Original ResearchLiver biopsyLiver tissueClinical practicePost-transplant complicationsRoutine clinical practiceTissue content analysisCommon indicationLiver diseaseNon-invasive methodMultiphoton microscopyHistologic evaluationMedical disordersEffective treatmentNew therapiesBiopsyClinical diagnosisClinical researchTissue samplesVisualization of tissuesTissue sectionsPrognostic capabilityClinical workflowImproved clinical diagnosisTissueDiagnosis
2019
Etiology of cirrhosis in the young
Olave MC, Gurung A, Mistry PK, Kakar S, Yeh M, Xu M, Wu TT, Torbenson M, Jain D. Etiology of cirrhosis in the young. Human Pathology 2019, 96: 96-103. PMID: 31698008, DOI: 10.1016/j.humpath.2019.09.015.Peer-Reviewed Original ResearchConceptsEtiology of cirrhosisCommon causeCryptogenic cirrhosisViral hepatitidesAge groupsMulti-institutional retrospective studyYears age group childrenIncidence of cirrhosisCause of cirrhosisFatty liver diseaseDiagnosis of cirrhosisAge group childrenCongenital cholestatic diseasesClinical chartsYounger patientsLiver diseasePathology databaseRetrospective studyCholestatic diseasePathology reportsCirrhosisMetabolic disordersPatientsScant dataYoung adultsCryptogenic cirrhosis: Old and new perspectives in the era of molecular and genomic medicine
Nalbantoglu I, Jain D. Cryptogenic cirrhosis: Old and new perspectives in the era of molecular and genomic medicine. Seminars In Diagnostic Pathology 2019, 36: 389-394. PMID: 31395291, DOI: 10.1053/j.semdp.2019.07.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCryptogenic cirrhosisCC casesLiver diseaseUnknown etiologyMain histologic findingsPossible genetic counselingChronic liver diseaseWhole-exome sequencingCirrhosis casesPediatric patientsTransplant eligibilityHistologic findingsHistologic patternPotential etiologiesHistologic examinationHistologic characterizationGenetic testingEtiologyPatientsExome sequencingDiagnostic abilityGenetic counselingGenetic alterationsDiagnosisNew disorderClinical utility of genomic analysis in adults with idiopathic liver disease
Hakim A, Zhang X, DeLisle A, Oral EA, Dykas D, Drzewiecki K, Assis DN, Silveira M, Batisti J, Jain D, Bale A, Mistry PK, Vilarinho S. Clinical utility of genomic analysis in adults with idiopathic liver disease. Journal Of Hepatology 2019, 70: 1214-1221. PMID: 31000363, PMCID: PMC6526061, DOI: 10.1016/j.jhep.2019.01.036.Peer-Reviewed Original ResearchConceptsIdiopathic liver diseaseUnexplained liver diseaseManagement of adultsWhole-exome sequencingLiver diseaseAdult patientsUnknown etiologyHeterozygous variantsUse of WESAmelioration of dyslipidemiaDaily insulin requirementLeptin replacement therapyUtility of WESChronic liver diseaseNon-alcoholic steatohepatitisAcademic health care centerHealth care centersHomozygous pathogenic variantUnrelated adult patientsNon-oncological diseasesDisease preventive measuresInsulin requirementsLean patientsDevastating complicationLiver aminotransferasesRecessive Mutations in KIF12 Cause High Gamma‐Glutamyltransferase Cholestasis
Aksu A, Das SK, Nelson‐Williams C, Jain D, Hoşnut F, Şahin G, Lifton RP, Vilarinho S. Recessive Mutations in KIF12 Cause High Gamma‐Glutamyltransferase Cholestasis. Hepatology Communications 2019, 3: 471-477. PMID: 30976738, PMCID: PMC6442693, DOI: 10.1002/hep4.1320.Peer-Reviewed Original ResearchLiver diseaseHigh GGTUndiagnosed liver diseaseHomozygous mutationCholestatic liver diseaseUnmet medical needWhole-exome sequencingSame homozygous mutationPediatric hepatologyNeonatal cholestasisRare homozygous mutationUnclear etiologyCholestasisUndiagnosed childrenMedical needUnrelated childrenGermline DNADiseaseMember 12ChildrenConsanguineous unionsOlder siblingsMissense mutationsGGTDamaging mutationsIdentification of key challenges in liver pathology: data from a multicenter study of extramural consults
Torbenson MS, Arnold CA, Graham RP, Jain D, Kakar S, Lam-Himlin DM, Naini BV, Wu TT, Yeh M. Identification of key challenges in liver pathology: data from a multicenter study of extramural consults. Human Pathology 2019, 87: 75-82. PMID: 30857968, DOI: 10.1016/j.humpath.2019.03.001.Peer-Reviewed Original ResearchConceptsLiver pathologyEtiology of cirrhosisFatty liver diseasePrimary biliary cirrhosisDiagnosis of malignancyFocal nodular hyperplasiaLiver casesAutoimmune hepatitisHepatitic patternBiliary cirrhosisLiver diseaseMetastatic malignancyMulticenter studyHepatic adenomaNodular hyperplasiaBenign tumorsConsult serviceMalignant tumorsHepatocellular carcinomaAcademic centersSpecific diagnosisTumor pathologyTumor typesConsultant diagnosesPatient care
2018
A practical diagnostic approach to hepatic masses.
Vyas M, Jain D. A practical diagnostic approach to hepatic masses. Indian Journal Of Pathology And Microbiology 2018, 61: 2-17. PMID: 29567877, DOI: 10.4103/ijpm.ijpm_578_17.Peer-Reviewed Original ResearchConceptsDifferential diagnosisHepatic massCorrect diagnosisRight diagnosisBackground liver diseaseUnknown primary siteFocal nodular hyperplasiaHepatic mass lesionsPractical diagnostic approachList of antibodiesNonhepatocellular originProper workupClinical presentationHepatocellular originLiver diseaseHistologic featuresPrimary lesionClinicopathological correlationHepatic adenomaVascular tumorsMass lesionNonepithelial neoplasmsCommon siteNeedle biopsyNodular hyperplasia
2017
Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response
Cai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017, 2: e90780. PMID: 28289714, PMCID: PMC5333973, DOI: 10.1172/jci.insight.90780.Peer-Reviewed Original ResearchConceptsLiver injuryInflammatory responseBile acid-induced liver injuryCholestatic liver injuryInflammatory liver injuryProinflammatory cytokine expressionCholestatic liver diseaseBile duct ligationVivo mouse modelHepatic infiltrationInflammatory injurySerum aminotransferasesLiver diseaseCholestatic patientsCytokine expressionChemokine inductionPathophysiologic concentrationsNeutrophil chemotaxisDuct ligationPathophysiologic levelsMouse modelNew therapiesInnate immunityInjuryPeriportal areas
2016
Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension
Vilarinho S, Sari S, Yilmaz G, Stiegler AL, Boggon TJ, Jain D, Akyol G, Dalgic B, Günel M, Lifton RP. Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension. Hepatology 2016, 63: 1977-1986. PMID: 26874653, PMCID: PMC4874872, DOI: 10.1002/hep.28499.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceAnimalsCattleChildChild, PreschoolDNA Mutational AnalysisDogsFemaleGenes, RecessiveHomozygoteHumansHypertension, PortalInfantLiver FailureMaleMolecular Sequence DataPedigreePhosphotransferases (Alcohol Group Acceptor)Principal Component AnalysisRatsYoung AdultConceptsIdiopathic noncirrhotic portal hypertensionNoncirrhotic portal hypertensionPortal hypertensionHuman immunodeficiency viral infectionNoncirrhotic liver diseaseStable portal hypertensionSubset of patientsTreatment of patientsNucleoside analog didanosineLiver failureIndeterminate etiologyLiver diseaseHypertensionKinase levelsNew genetic testsViral infectionMechanisms mediatingDGUOK deficiencyPhenotypic spectrumSpecific causesDeoxyguanosine kinaseExome sequencingPatientsConsanguineous familyFunction mutations