Review for 10.1186/1471-230X-2-21 (2002)

Reviewer's□report 
□The□liver□is□a□common□extra-glandular□target□in□primary□Sjogren's□syndrome:□A□retrospective□ Title: 
review 
Authors: 
Mariana□J□Kaplan□( makaplan@umich.edu )
Robert□W□Ike□( rike@umich.edu )
□1□ □27□May□2002 Version: Date: 
□Dr□Anne□Marie□Pedersen Reviewer: 
□A□paper□of□limited□interest Level□of□interest: 
□Unable□to□decide□on□acceptance□or□rejection□until□the□authors□have□responded□ Advice□on□publication: 
to□the□compulsory□revisions 
aEoeThe□liver□is□a□common□extra-glandular□target□in□primary□SjogrenaETMs□syndrome:□A□retrospective□ 
reviewaE□by□Kaplan□MJ□and□Ike□RW□ 
The□aim□of□this□retrospective□study□including□73□charts□of□patients□fulfilling□the□EEC□criteria□for□primary□ 
SjogrenaETMs□syndrome□(pSS)□was□to□determine□the□prevalence□of□liver□dysfunction□in□pSS□and□to□ 
evaluate□the□association□of□this□dysfunction□with□other□extra-glandular□disease□manifestations□as□well□as 
with□serological□markers□of□autoimmunity□and□systemic□inflammation.□The□results□indicate□that□liver□ 
involvement□is□the□most□common□extra-glandular□disease□manifestation□in□pSS.□Furthermore,□a□positive□ 
correlation□between□the□presence□of□liver□disease□and□other□extra-glandular□manifestations□was□also□ 
demonstrated□as□well□as□an□association□between□liver□disease□and□elevated□sedimentation□rate□and□a□ 
positive□ENA.□The□authors□conclude□that□an□evaluation□for□clinical□and□serological□evidence□of□liver□ disease□should□be□performed□in□every□patient□with□pSS□and□especially□in□those□with□other□ 
extra-glandular□disease□manifestations□or□serological□evidence□of□systemic□inflammation.□ 
I□appreciate□the□fact□that□this□is□a□retrospective□study,□but□the□design□is□fundamentally□flawed□which□ 
severely□limits□the□value□of□the□results.□Retrospective□studies□are□not□usually□suitable□for□determination□ 
of□prevalence.□In□this□respect,□determination□of□the□true□prevalence□of□liver□involvement□in□pSS□would□ 
require□a□standardized□clinical□and□serological□evaluation□with□regard□to□liver□function□in□each□patient□ included□in□the□study.□Moreover,□a□serious□limitation□of□this□retrospective□study□is□that□the□diagnosis□of□ pSS□appearently□is□made□at□the□time□the□study□is□established.□Accordingly,□information□that□forms□the□ 
basis□of□selection□of□cases□is□extremely□important.□It□is□stated□that□115□charts□of□patients□with□pSS□were□ 
reviewed□and□that□73□of□these□cases□fulfilling□the□EEC□criteria□for□the□diagnosis□of□pSS□were□further□ analyzed.□However,□it□is□unclear□whether□the□EEC□diagnostic□criteria□solely□formed□the□basis□of□ selection.□Futhermore,□it□should□be□stated□how□many□of□the□selected□73□patients□had□subjective□ 
symptoms□and□how□many□had□objective□findings□including□keratoconjunctivitis□sicca,□positive□labial□ 
salivary□gland□biopsy,□sero-positivity□and/or□salivary□gland□hypofunction.□What□indicated□serological□ evaluation□of□liver□function□in□the□59□cases?□Information□concerning□the□criteria□used□for□diagnosing□the□ remaining□42□cases□who□had□pSS□would□also□be□interesting□in□order□to□determine□in□what□way□they□ 
differed□from□the□73□cases.□In□general,□the□authors□should□clearly□describe□the□variables□that□were□ 
recorded□reviewing□the□charts□since□the□risk□of□selection□bias□is□obvious.□ 
The□73□patients□included□in□this□study□are□insufficiently□characterized□e.g.□there□is□no□information□ 
concerning□age□at□time□of□onset□of□disease,□disease□duration,□smoking□habits□(smoking□patients□have□a□ lower□frequency□of□focal□lymphocytic□infiltrates),□or□medication□etc.□Furthermore,□throughout□the□paper□ there□is□an□inconsistent□use□of□various□terms□for□liver□involvement□i.e.,□liver□dysfunction,□liver□disease□ 
and□clinical□hepatic□disease.□An□exact□definition□of□each□term□should□be□given,□i.e.,□how□do□the□authors□ 
define□aEoeclinical□evidence□of□liver□dysfunctionaE?□Also□the□terms□extra-glandular□and□sicca□(Table□2)□ should□be□defined.□The□latter□terms□are□imprecise□and□should□be□avoided□since□aEoesiccaaE□implies□ dryness□which□is□not□necessarily□a□feature□of□all□glandular□manifestations,□and□not□all□extra-glandular□ 
manifestations□are□systemic.□The□more□recent□proposed□terms□aEoeexocrineaE□and□ 
aEoenon-exocrineaE□are□more□exact.□ 
The□section□aEoeMethodsaE□should□include□the□number□of□charts□of□patients□reviewed,□the□number□of□ 
patients□included□as□well□as□a□table□comprising□the□clinical□and□serological□characteristics□of□the□ 
patients.□The□authors□state□that□the□statistical□analysis□includes□means,□standard□deviations□and□ranges. However,□these□measures□are□not□mentioned□in□the□text□or□in□the□tables.□In□fact,□only□one□value□is□given□ and□that□is□the□median□(!)□value□of□age□in□the□section□aEoeResultsaE.□Table□1□is□imprecise□and□it□is□ 
unclear□whether□aEoeclinical□featuresaE□only□represent□the□extra-glandular□disease□manifestations.□ 
RaynaudaETMs□phenomenon□as□well□as□other□frequent□disease□manifestations□such□as□those□of□the□ musculo-skeletal□system□and□endocrine□system□are□not□mentioned.□In□Table□2□the□total□number□of□ 
patients□should□be□stated□(basis□of□calculations)□and□the□term□aEoesiccaaE□defined.□The□type□of□disease 
manifestations□within□the□groups□aEoesiccaaE□and□aEoeliveraE□should□be□specified□as□they□have□been□ 
specified□for□the□other□groups□of□organ□systems.□The□frequency□of□liver□involvement□is□apparently□ 
calculated□from□the□59□cases□whereas□the□frequencies□of□the□remaining□organ□involvements□are□based□ 
on□the□73□cases□thereby□making□comparision□improper.□In□general,□the□magnitude□and□order□in□ 
prevalencies□of□disease□manifestations□given□in□this□table□are□not□in□keeping□with□previous□observations. 
According□to□the□section□aEoeResultsaE□73□cases□were□included□in□the□study□but□according□to□the□ 
parenthesis□it□is□74□cases□(56□women□and□18□men).□Later□in□the□same□section□it□is□stated□that□49.1%□had 
abnormal□liver□function□tests□but□according□to□Table□2□it□is□49.2%?□Table□3□lacks□number□of□patients□ 
studied□and□should□also□include□mean□values,□standard□deviations□and/or□ranges.□The□same□holds□true□ 
for□Table□4.□Concerning□the□figures□the□text□should□also□be□more□precise/detailed.□In□general,□the□limited□ 
number□of□pSS□patients□with□liver□involvement□make□analysis□for□associations□between□single□disease□ 
manifestations□and□serological□parametres□inappropriate.□ 
In□conclusion,□I□cannot□recommend□publication□of□this□manuscript□until□the□comments□above□are□dealt□ 
with.□ 
Competing□interests: 
None□declared.