Background_NNP Primary_JJ Sjögren_NNP 's_POS syndrome_NN (_( 1_CD °_NN SS_NNP )_) is_VBZ a_DT systemic_JJ autoimmune_JJ disorder_NN characterized_VBN by_IN dry_JJ eyes_NNS (_( keratoconjunctivitis_NNS sicca_NN )_) ,_, dry_JJ mouth_NN (_( xerostomia_NN )_) as_RB well_RB as_IN involvement_NN of_IN other_JJ exocrine_NN glands_NNS ._. 
While_IN 1_CD °_NN SS_NNP is_VBZ typically_RB considered_VBN an_DT autoimmune_JJ exocrinopathy_NN ,_, the_DT immune_JJ destruction_NN can_MD often_RB extend_VB to_TO affect_VB non-exocrine_JJ organs_NNS ._. 
Around_IN 25_CD %_NN of_IN patients_NNS with_IN 1_CD °_NN SS_NNP can_MD present_VB with_IN involvement_NN of_IN other_JJ organs_NNS such_JJ as_IN the_DT thyroid_NN ,_, central_JJ nervous_JJ system_NN ,_, lungs_NNS ,_, kidney_NN and_CC liver_NN ._. 
The_DT association_NN of_IN liver_NN disease_NN and_CC 1_CD °_NN SS_NNP was_VBD suggested_VBN more_JJR than_IN 40_CD years_NNS ago_RB [_NN 1_CD ]_NN ._. 
While_IN liver_NN involvement_NN in_IN 1_CD °_NN SS_NNP has_VBZ been_VBN considered_VBN "_'' rare_JJ "_'' [_NN 2_CD ]_NN only_RB a_DT few_JJ clinical_JJ studies_NNS specifically_RB address_VBP this_DT complication_NN and_CC evaluate_VB the_DT association_NN of_IN liver_NN function_NN tests_VBZ abnormalities_NNS with_IN the_DT severity_NN of_IN 1_CD °_NN SS_NNP [_NN 3_CD 4_CD 5_CD 6_CD ]_NN ._. 

Liver_NNP diseases_NNS associated_VBN with_IN 1_CD °_NN SS_NNP include_VBP primary_JJ biliary_JJ cirrhosis_NNS (_( PBC_NNP )_) -_: autoimmune_JJ cholangitis_NNS [_NN 8_CD 9_CD 10_CD ]_NN ,_, autoimmune_JJ hepatitis_NN [_NN 5_CD 6_CD ]_NN ,_, viral_JJ hepatitis_NN (_( B_NNP and_CC C_NNP )_) [_NN 11_CD 12_CD 13_CD 14_CD 15_CD 16_CD 17_CD 18_CD 19_CD 20_CD 21_CD ]_NN ,_, sclerosing_VBG cholangitis_NNS [_NN 22_CD ]_NN ,_, and_CC nodular_NN regenerative_JJ hyperplasia_NN [_NN 23_CD ]_NN ._. 
In_IN addition_NN ,_, chronic_JJ lymphocytic_JJ sialadenitis_NNS has_VBZ been_VBN found_VBN in_IN patients_NNS with_IN different_JJ types_NNS of_IN liver_NN cirrhosis_NNS [_NN 16_CD 17_CD 18_CD 19_CD 20_CD 21_CD 22_CD 23_CD 24_CD ]_NN ._. 

We_PRP report_VBP the_DT results_NNS of_IN a_DT review_NN of_IN cases_NNS undertaken_VBN to_TO determine_VB the_DT prevalence_NN of_IN abnormal_JJ liver_NN function_NN tests_NNS (_( LFTs_NNP )_) and_CC liver_NN disease_NN in_IN patients_NNS with_IN 1_CD °_NN SS_NNP referred_VBD to_TO a_DT tertiary_JJ care_NN center_NN and_CC the_DT association_NN of_IN abnormal_JJ LFTs_NNP with_IN other_JJ systemic_JJ features_NNS and_CC autoimmunity_NN markers_NNS of_IN 1_CD °_NN SS_NNP ._. 

Methods_NNP Statistical_NNP analysis_NN The_DT statistical_JJ analysis_NN included_VBD descriptive_JJ measures_NNS (_( means_VBZ ,_, standard_JJ deviations_NNS and_CC ranges_NNS )_) ._. 
Comparison_NNP of_IN results_NNS of_IN patients_NNS with_IN and_CC without_IN liver_NN disease_NN was_VBD done_VBN using_VBG t-tests_JJ of_IN continuous_JJ variables_NNS and_CC Fisher_NNP 's_POS exact_JJ test_NN or_CC x_SYM 2_CD for_IN categoric_JJ measures_NNS ._. 

Results_NNS Of_IN the_DT 115_CD charts_NNS reviewed_VBN ,_, 73_CD cases_NNS (_( 55_CD women_NNS and_CC 18_CD men_NNS ,_, median_JJ age_NN 53_CD )_) fulfilled_VBN EECC_NNP for_IN 1_CD °_NN SS_NNP and_CC were_VBD initially_RB included_VBN for_IN analysis_NN ._. 
Of_IN the_DT 73_CD patients_NNS ,_, a_DT 54_CD %_NN of_IN them_PRP (_( 40_CD patients_NNS )_) have_VBP had_VBD a_DT salivary_JJ gland_NN biopsy_NN performed_VBN ._. 
In_IN all_PDT these_DT patients_NNS ,_, the_DT biopsy_NN confirmed_VBD the_DT diagnosis_NN of_IN Sjögren_NNP 's_POS syndrome_NN ._. 
All_DT patients_NNS studied_VBN had_VBD objective_NN evidence_NN of_IN 1_CD °_NN SS_NNP ,_, including_VBG keratoconjunctivitis_NNS sicca_NN ,_, positive_JJ labial_NN salivary_JJ gland_NN biopsy_NN ,_, autoantibodies_NNS and_CC /_NN or_CC salivary_JJ gland_NN hypofunction_NN ._. 
We_PRP excluded_VBD those_DT patients_NNS without_IN these_DT objective_NN criteria_NNS of_IN 1_CD °_NN SS_NNP and_CC also_RB those_DT who_WP did_VBD not_RB fulfill_VB EECC_NNP criteria_NNS ._. 

The_DT mean_JJ age_NN at_IN time_NN of_IN onset_NN of_IN disease_NN was_VBD 45_CD ±_NN 20.5_CD years_NNS old_JJ and_CC disease_NN duration_NN was_VBD 4.9_CD years_NNS ±_NN 4.5_CD years_NNS (_( mean_VB ±_NN range_NN )_) ._. 
Liver_NNP function_NN tests_NNS had_VBD been_VBN determined_VBN in_IN 59_CD patients_NNS (_( 80.8_CD %_NN )_) and_CC abnormal_JJ liver_NN function_NN tests_NNS were_VBD found_VBN in_IN 29_CD of_IN the_DT 59_CD patients_NNS (_( 49.1_CD %_NN )_) ._. 
Further_RB analysis_NN was_VBD then_RB undertaken_VBN in_IN those_DT patients_NNS in_IN whom_WP LFTs_NNP had_VBD been_VBN measured_VBN ._. 
The_DT clinical_JJ and_CC laboratory_NN characteristics_NNS of_IN these_DT patients_NNS are_VBP shown_VBN in_IN Tables_NNP 2_CD and_CC 3_CD ._. 

For_IN these_DT SS_NNP patients_NNS studied_VBN ,_, abnormal_JJ LFTs_NNP were_VBD more_RBR common_JJ than_IN any_DT other_JJ potential_JJ non-exocrine_JJ features_NNS of_IN SS_NNP ._. 
Clinical_NNP evidence_NN of_IN liver_NN disease_NN ,_, defined_VBN in_IN methods_NNS section_NN ,_, was_VBD found_VBN in_IN 12_CD patients_NNS (_( 20.3_CD %_NN )_) ,_, all_DT of_IN whom_WP had_VBD abnormal_JJ liver_NN function_NN tests_NNS ._. 
Two_CD deaths_NNS occurred_VBD in_IN the_DT population_NN studied_VBD ,_, both_DT attributed_VBD to_TO liver_NN failure_NN ._. 
An_DT additional_JJ patient_NN required_VBD a_DT liver_NN transplant_NN ._. 
In_IN all_DT cases_NNS ,_, the_DT diagnosis_NN of_IN 1_CD °_NN SS_NNP antedated_JJ the_DT onset_NN of_IN liver_NN disease_NN or_CC its_PRP$ diagnosis_NN ._. 
Markers_NNP of_IN viral_JJ hepatitis_NN ,_, sought_VBN in_IN 39_CD patients_NNS ,_, were_VBD found_VBN only_RB in_IN 4_CD ._. Two_CD patients_NNS carried_VBD the_DT surface_NN antigen_NN of_IN hepatitis_NNP B_NNP virus_NN and_CC one_CD had_VBD antibodies_NNS to_TO hepatitis_NNP C_NNP virus_NN ._. 
In_IN a_DT liver_NN biopsy_NN of_IN a_DT patient_NN who_WP lacked_VBD serological_JJ markers_NNS for_IN hepatitis_NN viruses_NNS ,_, hepatitis_NNP B_NNP virus_NN was_VBD detected_VBN by_IN in_IN situ_NN hybridization_NN ._. 

Risk_NN factors_NNS for_IN liver_NN disease_NN were_VBD identified_VBN in_IN 40_CD %_NN of_IN the_DT patients_NNS with_IN abnormal_JJ liver_NN function_NN tests_NNS and_CC are_VBP described_VBN in_IN Table_NNP 4_CD ._. No_DT association_NN with_IN tobacco_NN use_NN was_VBD found_VBN ._. 
Only_RB 5_CD patients_NNS had_VBD documented_VBN evidence_NN of_IN tobacco_NN consumption_NN ._. 
We_PRP found_VBD no_DT significant_JJ differences_NNS in_IN risk_NN factors_NNS for_IN abnormal_JJ liver_NN function_NN tests_NNS among_IN patients_NNS with_IN or_CC without_IN hepatic_JJ involvement_NN ._. 
Therefore_RB ,_, in_IN 60_CD %_NN of_IN the_DT patients_NNS with_IN sub_NN clinical_JJ or_CC clinical_JJ evidence_NN of_IN liver_NN disease_NN ,_, no_DT clear_JJ explanation_NN for_IN the_DT abnormal_JJ LFTs_NNP was_VBD found_VBN ,_, except_IN for_IN the_DT association_NN with_IN 1_CD °_NN SS_NNP ._. 

The_DT pattern_NN of_IN biochemical_JJ liver_NN abnormalities_NNS was_VBD mainly_RB hepatocellular_NN (_( defined_VBN as_IN predominant_NN increase_NN of_IN AST_NNP and_CC /_NN or_CC ALT_NNP in_IN comparison_NN with_IN AP_NNP and_CC /_NN or_CC bilirubins_NNS )_) in_IN 11_CD cases_NNS ;_: cholestatic_JJ (_( defined_VBN as_IN predominant_NN increase_NN in_IN AP_NNP and_CC /_NN or_CC bilirubins_NNS compared_VBN with_IN AST_NNP and_CC /_NN or_CC ALT_NNP )_) in_IN 3_CD and_CC mixed_JJ (_( evidence_NN of_IN both_DT cholestatic_JJ and_CC hepatocellular_NN damage_NN )_) in_IN 8_CD cases_NNS ._. 
Abnormalities_NNP were_VBD persistent_JJ (_( present_JJ on_IN every_DT occasion_NN when_WRB measured_VBN more_RBR than_IN once_RB )_) in_IN 19_CD patients_NNS (_( 65.5_CD %_NN of_IN those_DT with_IN abnormal_JJ LFTs_NNP )_) ,_, intermittent_JJ (_( presence_NN of_IN LFT_NNP abnormalities_NNS was_VBD not_RB found_VBN in_IN all_DT determinations_NNS )_) in_IN 9_CD (_( 31_CD %_NN )_) and_CC in_IN one_CD case_NN (_( 3.5_CD %_NN )_) there_EX was_VBD only_RB one_CD determination_NN of_IN liver_NN function_NN tests_NNS ._. 
The_DT pattern_NN of_IN liver_NN enzyme_NN abnormalities_NNS is_VBZ shown_VBN in_IN Figure_NN 1_CD ._. 
None_NN of_IN the_DT patients_NNS with_IN abnormal_JJ liver_NN function_NN tests_NNS had_VBD clinical_JJ evidence_NN of_IN muscle_NN involvement_NN that_WDT could_MD explain_VB the_DT high_JJ levels_NNS of_IN amino-transferases_JJ ._. 
Activity_NN of_IN CPK_NNP or_CC aldolase_NN was_VBD not_RB elevated_VBD when_WRB measured_VBN in_IN 15_CD of_IN the_DT 29_CD patients_NNS with_IN abnormal_JJ liver_NN function_NN tests_NNS ._. 
Anti-mitochondrial_NNP antibodies_NNS (_( AMA_NNP )_) and_CC anti-smooth_JJ muscle_NN antibodies_NNS (_( ASMA_NNP )_) were_VBD sought_VBN in_IN 5_CD patients_NNS ,_, with_IN positive_JJ ASMA_NNP in_IN 2_CD ._. 

The_DT association_NN of_IN abnormal_JJ liver_NN function_NN tests_NNS with_IN other_JJ non-exocrine_JJ features_NNS of_IN 1_CD °_NN SS_NNP is_VBZ shown_VBN in_IN Figure_NN 2_CD ._. Patients_NNS with_IN abnormal_JJ liver_NN function_NN tests_NNS were_VBD more_RBR likely_JJ to_TO have_VB lung_NN ,_, kidney_NN or_CC hematological_JJ manifestations_NNS ,_, when_WRB compared_VBN to_TO Sjögren_NNP 's_POS patients_NNS without_IN liver_NN disease_NN ._. 
Presence_NNP of_IN other_JJ non-exocrine_JJ features_NNS of_IN 1_CD °_NN SS_NNP was_VBD not_RB influenced_VBN by_IN prevalence_NN of_IN liver_NN diseases_NNS ._. 

Regarding_VBG laboratory_NN test_NN results_NNS ,_, patients_NNS with_IN liver_NN disease_NN were_VBD more_RBR likely_JJ to_TO have_VB an_DT elevated_JJ sedimentation_NN rate_NN at_IN some_DT point_NN during_IN the_DT course_NN of_IN their_PRP$ disease_NN ._. 
A_DT positive_JJ anti-_NN ENA_NNP (_( anti-_NN Ro_NNP ,_, anti-_NN Ro_NNP /_NN La_NNP ,_, and_CC /_NN or_CC anti-_NN RNP_NNP )_) was_VBD also_RB associated_VBN with_IN an_DT increased_JJ prevalence_NN of_IN abnormal_JJ liver_NN function_NN tests_NNS (_( Figure_NN 3_CD )_) ._. 
The_DT sample_NN was_VBD too_RB small_JJ to_TO determine_VB whether_IN a_DT specific_JJ ENA_NNP was_VBD associated_VBN with_IN liver_NN disease_NN ._. 
Other_JJ markers_NNS of_IN systemic_JJ inflammation_NN or_CC autoimmunity_NN did_VBD not_RB correlate_VBP with_IN the_DT presence_NN or_CC absence_NN of_IN LFT_NNP abnormalities_NNS ._. 

Liver_NNP biopsies_NNS ,_, done_VBN in_IN 8_CD patients_NNS ,_, disclosed_VBD post-viral_JJ chronic_JJ active_JJ hepatitis_NN (_( 3_CD )_) ,_, cryptogenic_JJ cirrhosis_NNS (_( 2_CD )_) ,_, and_CC one_CD case_NN each_DT of_IN post-viral_JJ cirrhosis_NNS ,_, alcoholic_JJ hepatitis_NN ,_, and_CC autoimmune_JJ hepatitis_NN ._. 

Discussion_NNP In_IN this_DT group_NN of_IN Sjögren_NNP 's_POS patients_NNS seen_VBN at_IN a_DT tertiary_JJ care_NN center_NN ,_, abnormal_JJ liver_NN function_NN tests_NNS were_VBD found_VBN to_TO be_VB a_DT common_JJ non-exocrine_JJ feature_NN of_IN 1_CD °_NN SS_NNP ._. 
The_DT prevalence_NN of_IN this_DT association_NN was_VBD found_VBN to_TO be_VB higher_JJR in_IN our_PRP$ study_NN than_IN in_IN other_JJ previous_JJ series_NN [_NN 2_CD 3_CD 4_CD 5_CD 6_CD 7_CD ]_NN ._. 
The_DT true_JJ prevalence_NN could_MD be_VB even_RB higher_JJR since_IN liver_NN enzyme_NN profiles_NNS were_VBD not_RB done_VBN in_IN all_DT patients_NNS ._. 
The_DT prevalence_NN suggested_VBD in_IN previous_JJ reports_NNS ranges_NNS from_IN 6_CD to_TO 58_CD %_NN ,_, but_CC the_DT definition_NN of_IN hepatic_JJ disease_NN varies_VBZ from_IN the_DT unspecific_JJ (_( e.g._NN hepatomegaly_RB )_) to_TO well_RB proven_VBN cases_NNS of_IN liver_NN disease_NN [_NN 1_CD 2_CD 3_CD 4_CD 5_CD 6_CD 7_CD 28_CD ]_NN ._. 
Denko_NNP in_IN 1960_CD reported_VBD that_IN 12_CD %_NN of_IN patients_NNS with_IN SS_NNP had_VBD hepatosplenomegaly_RB [_NN 29_CD ]_NN ._. 
Other_JJ studies_NNS done_VBN in_IN the_DT 1960_CD 's_POS also_RB confirmed_VBD hepatomegaly_RB in_IN 18_CD -_: 20_CD %_NN of_IN patients_NNS with_IN SS_NNP [_NN 30_CD 31_CD ]_NN ._. 
In_IN 1970_CD ,_, Whaley_NNP reported_VBD liver_NN disease_NN in_IN 6_CD %_NN of_IN patients_NNS with_IN SS_NNP and_CC mentioned_VBD an_DT association_NN with_IN anti-mitochondrial_JJ antibodies_NNS [_NN 2_CD ]_NN ._. 
In_IN 1986_CD ,_, Tsianos_NNP and_CC co-workers_NNS described_VBD 22_CD SS_NNP patients_NNS with_IN gastrointestinal_NN complications_NNS ,_, called_VBN from_IN a_DT large_JJ cohort_NN ;_: only_RB two_CD patients_NNS had_VBD liver_NN disease_NN ,_, each_DT with_IN chronic_JJ active_JJ hepatitis_NN [_NN 4_CD ]_NN ._. 
Other_JJ studies_NNS have_VBP reported_VBN variable_JJ prevalence_NN [_NN 3_CD 28_CD ]_NN and_CC different_JJ histopathological_JJ findings_NNS in_IN liver_NN biopsies_NNS ranging_VBG from_IN cholestatic_JJ liver_NN damage_NN (_( stage_NN I_PRP primary_JJ biliary_JJ cirrhosis_NNS )_) to_TO chronic_JJ active_JJ hepatitis_NN due_JJ to_TO hepatitis_NNP C_NNP virus_NN ._. 

In_IN our_PRP$ study_NN ,_, liver_NN disease_NN was_VBD associated_VBN with_IN other_JJ non-exocrine_JJ manifestations_NNS of_IN 1_CD °_NN SS_NNP ,_, specifically_RB those_DT affecting_VBG lung_NN ,_, kidney_NN and_CC blood_NN cells_NNS ._. 
Those_DT patients_NNS with_IN serological_JJ evidence_NN of_IN systemic_JJ inflammation_NN ,_, as_IN shown_VBN by_IN an_DT elevated_JJ sedimentation_NN rate_NN ,_, were_VBD more_RBR likely_JJ to_TO have_VB liver_NN test_NN abnormalities_NNS ._. 
Also_RB ,_, the_DT presence_NN of_IN a_DT positive_JJ anti-_NN ENA_NNP correlated_JJ positively_RB with_IN hepatic_JJ disease_NN ._. 
An_DT association_NN of_IN ENA_NNP response_NN with_IN liver_NN disease_NN has_VBZ been_VBN described_VBN in_IN children_NNS with_IN autoimmune_JJ hepatitis_NN ,_, where_WRB anti-_NN ENA-positive_NNP patients_NNS demonstrated_VBD more_RBR severe_JJ liver_NN test_NN abnormalities_NNS than_IN those_DT who_WP were_VBD anti-_NN ENA-negative_NNP [_NN 32_CD ]_NN ._. 
In_IN another_DT study_NN ,_, a_DT 15_CD %_NN of_IN patients_NNS with_IN various_JJ chronic_JJ liver_NN diseases_NNS were_VBD found_VBN to_TO be_VB anti-_NN RNP_NNP positive_JJ [_NN 33_CD ]_NN ._. 

With_IN etiopathogenesis_NNS of_IN 1_CD °_NN SS_NNP still_RB an_DT open_JJ question_NN [_NN 34_CD ]_NN ,_, a_DT possible_JJ role_NN of_IN hepatitis_NNP C_NNP virus_NN (_( HCV_NNP )_) has_VBZ drawn_VBN attention_NN ._. 
Recent_JJ studies_NNS have_VBP mentioned_VBN HCV_NNP incidence_NN in_IN patients_NNS with_IN 1_CD SS_NNP ranging_VBG from_IN 14_CD -_: 19_CD %_NN [_NN 11_CD 12_CD 16_CD 18_CD 21_CD ]_NN ._. 
Phenotypic_NNP characterization_NN of_IN the_DT minor_JJ salivary_JJ glands_NNS with_IN immunohistochemistry_NN in_IN patients_NNS with_IN hepatitis_NNP C_NNP virus_NN infection_NN and_CC /_NN or_CC 1_CD °_NN SS_NNP has_VBZ given_VBN conflicting_JJ results_NNS [_NN 14_CD 15_CD ]_NN Some_DT reports_NNS mention_VBP that_IN the_DT salivary_JJ gland_NN findings_NNS are_VBP strikingly_RB similar_JJ in_IN patients_NNS with_IN liver_NN disease_NN associated_VBN with_IN HCV_NNP infection_NN than_IN in_IN those_DT with_IN 1_CD °_NN SS_NNP [_NN 12_CD ]_NN ,_, while_IN others_NNS mention_VBP distinctive_JJ differences_NNS between_IN both_DT groups_NNS regarding_VBG focus_NN score_NN ,_, expression_NN of_IN surface_NN markers_NNS in_IN lymphocytes_NNS infiltrating_VBG the_DT salivary_JJ glands_NNS and_CC in_IN epithelial_NN cells_NNS ,_, as_RB well_RB as_IN differences_NNS in_IN the_DT degree_NN of_IN inflammation_NN [_NN 14_CD 15_CD ]_NN ._. 
Transgenic_NNP mice_NNS models_NNS that_WDT carry_VBP the_DT HCV_NNP envelope_NN genes_NNS develop_VBP an_DT exocrinopathy_NN affecting_VBG salivary_JJ and_CC lachrymal_NN glands_NNS [_NN 19_CD ]_NN ._. 
Expression_NNP of_IN autoimmunity_NN markers_NNS also_RB tends_VBZ to_TO differ_VB between_IN HCV-infection_NN and_CC 1_CD °_NN SS_NNP ._. 
Positive_JJ ENAs_NNP are_VBP rarely_RB seen_VBN in_IN HCV-patients_NNP ._. 
Also_RB ,_, in_IN most_JJS cases_NNS sicca_NN symptoms_NNS are_VBP not_RB present_JJ in_IN individuals_NNS with_IN HCV_NNP as_IN compared_VBN with_IN the_DT 1_CD °_NN SS_NNP population_NN ._. 
Although_IN the_DT prevalence_NN of_IN viral_JJ hepatitis_NN markers_NNS in_IN our_PRP$ group_NN of_IN patients_NNS with_IN liver_NN disease_NN was_VBD very_RB low_JJ and_CC did_VBD not_RB account_VB for_IN most_JJS of_IN the_DT cases_NNS with_IN abnormal_JJ liver_NN function_NN tests_NNS ,_, these_DT markers_NNS were_VBD not_RB sought_VBN in_IN a_DT small_JJ percentage_NN of_IN these_DT patients_NNS ._. 
It_PRP is_VBZ important_JJ to_TO note_VB that_IN HCV_NNP appears_VBZ to_TO account_VB for_IN a_DT subgroup_NN of_IN patients_NNS with_IN exocrine_NN complaints_NNS in_IN which_WDT half_PDT the_DT cases_NNS might_MD meet_VB the_DT definition_NN for_IN SS_NNP according_VBG to_TO European_JJ and_CC Manthorpe_NNP criteria_NNS ._. 
However_RB ,_, this_DT subgroup_NN is_VBZ characterized_VBN by_IN the_DT absence_NN of_IN clinical_JJ manifestations_NNS observed_VBD in_IN 1_CD °_NN SS_NNP ,_, and_CC the_DT absence_NN of_IN anti-_NN Ro_NNP and_CC anti-_NN La_NNP [_NN 35_CD ]_NN ._. 

An_DT aberrant_NN interaction_NN between_IN lymphocytes_NNS and_CC different_JJ epithelial_NN tissues_NNS has_VBZ been_VBN proposed_VBN as_IN a_DT mechanism_NN for_IN the_DT damage_NN seen_VBN in_IN different_JJ organs_NNS in_IN 1_CD °_NN SS_NNP [_NN 36_CD ]_NN ._. 
Since_IN it_PRP has_VBZ been_VBN suggested_VBN that_IN the_DT target_NN tissue_NN involved_VBN in_IN the_DT autoimmune_JJ histopathologic_JJ lesions_NNS of_IN 1_CD °_NN SS_NNP might_MD be_VB the_DT epithelium_NN [_NN 37_CD ]_NN ,_, it_PRP is_VBZ interesting_JJ that_IN the_DT findings_NNS in_IN our_PRP$ study_NN point_NN to_TO the_DT association_NN of_IN liver_NN disease_NN with_IN pulmonary_JJ and_CC renal_JJ abnormalities_NNS ,_, all_DT which_WDT are_VBP characterized_VBN by_IN epithelial_NN damage_NN [_NN 38_CD 39_CD ]_NN ._. 
Epithelial_NNP cells_NNS have_VBP been_VBN proposed_VBN to_TO be_VB active_JJ participants_NNS rather_RB than_IN passive_JJ targets_NNS in_IN the_DT chronic_JJ immune_JJ response_NN in_IN 1_CD °_NN SS_NNP but_CC further_JJ studies_NNS are_VBP needed_VBN to_TO establish_VB the_DT role_NN of_IN liver_NN epithelial_NN cells_NNS in_IN the_DT pathogenesis_NNS of_IN hepatic_JJ damage_NN in_IN this_DT disease_NN ,_, including_VBG the_DT analysis_NN of_IN HLA_NNP expression_NN and_CC cytokine_NN secretion_NN pattern_NN in_IN these_DT cells_NNS ._. 

The_DT co-existence_NN of_IN liver_NN disease_NN and_CC the_DT presence_NN of_IN circulating_VBG AMAs_NNP in_IN Sjögren_NNP 's_POS patients_NNS sera_NN has_VBZ been_VBN pointed_VBN as_IN an_DT indicator_NN that_DT liver_NN pathology_NN might_MD be_VB autoimmune_JJ and_CC similar_JJ to_TO that_DT of_IN primary_JJ biliary_JJ cirrhosis_NNS [_NN 4_CD 7_CD 8_CD 10_CD ]_NN ._. 
In_IN previous_JJ studies_NNS ,_, a_DT pericholangial_NN lymphocytic_JJ infiltration_NN similar_JJ to_TO that_DT found_VBD in_IN stage_NN I_PRP of_IN primary_JJ biliary_JJ cirrhosis_NNS ,_, has_VBZ been_VBN reported_VBN in_IN 1_CD °_NN SS_NNP with_IN abnormal_JJ liver_NN function_NN tests_NNS or_CC positivity_NN for_IN AMA_NNP [_NN 4_CD 7_CD ]_NN ._. 
In_IN our_PRP$ review_NN of_IN cases_NNS ,_, we_PRP found_VBD predominance_NN in_IN hepatocellular_NN liver_NN damage_NN rather_RB than_IN cholestatic_JJ disease_NN ,_, which_WDT would_MD argue_VB against_IN a_DT PBC-type_NNP of_IN liver_NN damage_NN ._. 
Other_JJ authors_NNS had_VBD proposed_VBN that_IN SS_NNP associated_VBN with_IN PBC_NNP should_MD be_VB considered_VBN a_DT form_NN of_IN secondary_JJ SS_NNP that_WDT resembles_VBZ more_JJR the_DT "_'' sicca_NN complex_JJ "_'' with_IN exocrine_NN features_NNS seen_VBN in_IN patients_NNS with_IN rheumatoid_NN arthritis_NN [_NN 40_CD 41_CD ]_NN ._. 

Limitations_NNPS of_IN the_DT study_NN come_VB primarily_RB from_IN being_VBG a_DT retrospective_NN analysis_NN ._. 
Since_IN the_DT patients_NNS were_VBD studied_VBN in_IN a_DT tertiary_JJ care_NN referral_NN center_NN ,_, the_DT severity_NN of_IN the_DT disease_NN and_CC the_DT prevalence_NN of_IN the_DT manifestations_NNS might_MD be_VB different_JJ from_IN the_DT general_JJ 1_CD °_NN SS_NNP population_NN ._. 
Furthermore_RB ,_, in_IN many_JJ cases_NNS ,_, Sjögren_NNP 's_POS syndrome_NN diagnosis_NN had_VBD been_VBN sought_VBN because_IN of_IN otherwise_RB unexplained_JJ non-exocrine_JJ features_NNS ._. 
While_IN we_PRP could_MD not_RB find_VB an_DT association_NN between_IN use_NN of_IN NSAIDS_NNP or_CC other_JJ medications_NNS and_CC prevalence_NN of_IN liver_NN function_NN tests_VBZ abnormalities_NNS ,_, the_DT study_NN design_NN did_VBD not_RB allow_VB us_PRP to_TO exclude_VB the_DT possibility_NN of_IN over-the-counter_JJ (_( OTC_NNP )_) medication_NN use_NN that_WDT could_MD have_VB affected_VBN LFT_NNP 's_POS measurement_NN ._. 
Drug_NN toxicity_NN is_VBZ certainly_RB an_DT important_JJ factor_NN to_TO be_VB considered_VBN ._. 
However_RB ,_, given_VBN that_IN most_JJS patients_NNS had_VBD persistent_JJ rather_RB than_IN intermittent_JJ abnormalities_NNS of_IN LFTs_NNP and_CC that_IN the_DT use_NN of_IN hepatotoxic_JJ drugs_NNS was_VBD not_RB elicited_JJ in_IN the_DT majority_NN of_IN patients_NNS with_IN liver_NN abnormalities_NNS ,_, a_DT toxic_JJ effect_NN of_IN medications_NNS could_MD not_RB be_VB established_VBN ._. 

Conclusions_NNP Based_VBN on_IN the_DT results_NNS of_IN this_DT study_NN ,_, we_PRP consider_VBP that_IN an_DT evaluation_NN for_IN clinical_JJ and_CC serological_JJ evidence_NN of_IN liver_NN disease_NN should_MD be_VB done_VBN in_IN every_DT patient_NN with_IN 1_CD °_NN SS_NNP ,_, particularly_RB if_IN there_EX is_VBZ evidence_NN of_IN other_JJ non-exocrine_JJ complications_NNS or_CC serological_JJ evidence_NN of_IN systemic_JJ inflammation_NN ._. 
Although_IN no_DT other_JJ diagnosis_NN explaining_VBG liver_NN disease_NN may_MD be_VB found_VBN ,_, the_DT disorders_NNS for_IN which_WDT treatment_NN might_MD be_VB beneficial_JJ (_( e.g._NN immunosuppressants_NNS for_IN autoimmune_JJ hepatitis_NN ,_, interferon-alpha_JJ for_IN viral_JJ hepatitis_NN ,_, ursodeoxycolic_JJ acid_NN for_IN primary_JJ biliary_JJ cirrhosis_NNS )_) warrant_NN a_DT diligent_NN search_NN in_IN all_DT cases_NNS of_IN 1_CD °_NN SS_NNP with_IN abnormal_JJ liver_NN function_NN ._. 

Competing_VBG interests_NNS None_NN ._. 
Authors_NNP '_POS contributions_NNS Both_DT authors_NNS contributed_VBD equally_RB to_TO the_DT paper_NN ._. 

