title: Prevalence and risk factors for liver involvement in individuals with PiZZ-related lung disease.
abstract: BACKGROUND
  α1-Antitrypsin deficiency is one of the most common heritable human diseases, predisposing to liver and lung injury. Significant heterogeneity in phenotypic expression is well documented, but less is known of the prevalence, severity, and correlates of chronic liver disease among individuals presenting with lung disease.
  
  
  OBJECTIVE
  To determine the frequency of and risk factors for severe liver fibrosis and cirrhosis among individuals with PiZZ-related lung disease.
  
  
  METHODS
  A well-characterized cohort of 57 PiZZ adults attending a tertiary referral respiratory clinic was screened prospectively for clinical, laboratory, radiologic, and (when appropriate) histologic evidence of chronic liver disease.
  
  
  RESULTS
  Thirty-six (63.2%) of 57 had a history or clinical findings suggestive of liver disease; or had one or more abnormalities of liver function, or liver ultrasound, and 24 of these underwent liver biopsy. Ten (17.5%) had evidence of severe fibrosis or cirrhosis and were more likely to have higher body mass index (P = 0.04), alanine transaminase (P = 0.0001), alkaline phosphatase (P = 0.0009), prothrombin time (P = 0.0005), and maximal vital capacity (VCmax) (P = 0.04); lower platelet count (P = 0.007); abnormal liver echogenicity (P < 0.001); and splenomegaly (P = 0.001) at ultrasound. Screening with liver ultrasound provided a sensitivity and negative predictive value for severe fibrosis or cirrhosis of 100%, as were the specificity and positive predictive value for platelet count less than or equal to 174,000 per mm(3) and splenomegaly. Among individuals undergoing liver biopsy, fibrosis stage correlated with increasing VCmax (P = 0.02) and % predicted VCmax (P = 0.05), and decreasing residual volume/total lung capacity (TLC) (P = 0.02) and % predicted residual volume/TLC (P = 0.05).
  
  
  CONCLUSIONS
  Significant chronic liver disease is common in PiZZ individuals with lung disease and can be screened effectively by a combination of conventional tests of liver function, platelet count, and liver ultrasound.
authors.affiliation: Liver Unit, Box 210, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. drdawwas@gmail.com
authors.forename: Muhammad F
authors.initials: MF
authors.lastname: Dawwas
authors.forename: Susan E
authors.initials: SE
authors.lastname: Davies
authors.forename: William J H
authors.initials: WJ
authors.lastname: Griffiths
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Alexander
mesh_terms: D000328:Adult; D015415:Biomarkers; D002908:Chronic Disease; D015897:Comorbidity; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010976:Platelet Count; D015995:Prevalence; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014463:Ultrasonography; D006113:United Kingdom / Q000453:epidemiology; D019896:alpha 1-Antitrypsin Deficiency / Q000453:epidemiology*
chemical_list: D015415:Biomarkers