title: Chronic hepatitis C virus infection: prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients.
abstract: OBJECTIVE
  To assess the prevalence of extrahepatic manifestations in Bulgarian patients with chronic hepatitis C virus (HCV) infection and identify the clinical and biological manifestations associated with cryoglobulinemia.
  
  
  METHODS
  The medical records of 136 chronically infected HCV patients were reviewed to assess the prevalence of extrahepatic manifestations. Association between cryoglobulin-positivity and other manifestations were identified using chi2 and Fisher's exact test. Risk factors for the presence of extrahepatic manifestations were assessed by logistic regression analysis.
  
  
  RESULTS
  Seventy six percent (104/136) of the patients had at least one extrahepatic manifestation. Clinical manifestations included fatigue (59.6%), kidney impairment (25.0%), type 2 diabetes (22.8%), paresthesia (19.9%), arthralgia (18.4%), palpable purpura (17.6%), lymphadenopathy (16.2%), pulmonary fibrosis (15.4%), thyroid dysfunction (14.7%), Raynaud's phenomenon (11.8%), B-cell lymphoma (8.8%), sicca syndrome (6.6%), and lichen planus (5.9%). The biological manifestations included cryoglobulin production (37.5%), thrombocytopenia (31.6%), and autoantibodies: anti-nuclear (18.4%), anti-smooth muscle (16.9%), anti-neutrophil cytoplasm (13.2%) and anti-cardiolipin (8.8%). All extrahepatic manifestations showed an association with cryoglobulin-positivity, with the exception of thyroid dysfunction, sicca syndrome, and lichen planus. Risks factors for the presence of extrahepatic manifestations (univariate analysis) were: age > or = 60 years, female gender, virus transmission by blood transfusions, longstanding infection (> or = 20 years), and extensive liver fibrosis. The most significant risks factors (multivariate analysis) were longstanding infection and extensive liver fibrosis.
  
  
  CONCLUSIONS
  We observed a high prevalence of extrahepatic manifestations in patients with chronic HCV infection. Most of these manifestations were associated with impaired lymphoproliferation and cryoglobulin production. Longstanding infection and extensive liver fibrosis were significant risk factors for the presence of extrahepatic manifestations in HCV patients.
authors.affiliation: Department of Internal Diseases and Gastroenterology, University Hospital Alexandrovska, 1, Georgi Sofiiski Str, Sofia 1431, Bulgaria. d.petrova.stefanova@gmail.com
authors.forename: Diana V
authors.initials: DV
authors.lastname: Stefanova-Petrova
authors.forename: Anelia H
authors.initials: AH
authors.lastname: Tzvetanska
authors.forename: Elisaveta J
authors.initials: EJ
authors.lastname: Naumova
authors.forename: Anastasia P
authors.initials: AP
authors.lastname: Mihailova
authors.forename: Evgenii A
authors.initials: EA
authors.lastname: Hadjiev
authors.forename: Rumiana P
authors.initials: RP
authors.lastname: Dikova
authors.forename: Mircho I
authors.initials: MI
authors.lastname: Vukov
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Tchernev
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002031:Bulgaria / Q000453:epidemiology; D003449:Cryoglobulinemia / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D016015:Logistic Models; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies