title: Extrahepatic Manifestations of Hepatitis C: A Meta-analysis of Prevalence, Quality of Life, and Economic Burden.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) infection has hepatic and extrahepatic manifestations with various costs and impairments to health-related quality of life (HRQL). We performed a meta-analysis to determine the prevalence of extrahepatic manifestations in patients with HCV infection, how these impair HRQL, and their costs.
  
  
  METHODS
  We performed systematic reviews of the literature using MEDLINE, CINAHL, and the Cochrane Systematic Review Database, from 1996 through December 2014, to identify studies of the following extrahepatic manifestations of HCV infection: mixed cryoglobulinemia, chronic kidney or end-stage renal disease, type 2 diabetes, B-cell lymphoma, lichen planus, Sjögren's syndrome, porphyria cutanea tarda, rheumatoid-like arthritis, or depression. We performed a separate meta-analysis for each condition to determine prevalence rates of extrahepatic manifestations of HCV infection and their effects on HRQL. We determined the annual costs (inpatient, outpatient, and pharmacy) associated with extrahepatic manifestations of HCV infection.
  
  
  RESULTS
  In an analysis of data from 102 studies, we found the most common extrahepatic manifestations to be diabetes (in 15% of patients) and depression (in 25% of patients). HRQL data showed that HCV infection had negative effects on overall physical and mental health. Total direct medical costs of extrahepatic manifestations of HCV infection, in 2014 US dollars, were estimated to be $1506 million (range, $922 million-$2208 million in sensitivity analysis).
  
  
  CONCLUSIONS
  In a systematic review and meta-analysis we determined the prevalence, risks, and costs associated with extrahepatic manifestations of HCV infection. These estimates should be added to the liver-related burden of disease to obtain a more accurate assessment of the total burden of chronic HCV infection. Prospective, real-world studies are needed to increase our understanding of the total clinical and economic effects of HCV infection and treatment on patients and society.
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia; Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia. Electronic address: zobair.younossi@inova.org.
authors.forename: Zobair
authors.initials: Z
authors.lastname: Younossi
authors.affiliation: University of Florida College of Pharmacy, Gainesville, Florida.
authors.forename: Haesuk
authors.initials: H
authors.lastname: Park
authors.affiliation: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia.
authors.forename: Linda
authors.initials: L
authors.lastname: Henry
authors.affiliation: University of Florida College of Pharmacy, Gainesville, Florida.
authors.forename: Ayoade
authors.initials: A
authors.lastname: Adeyemi
authors.affiliation: Center for Outcomes Research in Liver Diseases, Washington, District of Columbia.
authors.forename: Maria
authors.initials: M
authors.lastname: Stepanova
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000821:virology; D017281:Cost of Illness; D003449:Cryoglobulinemia / Q000453:epidemiology / Q000821:virology; D003863:Depression / Q000453:epidemiology / Q000821:virology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000821:virology; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000191:economics* / Q000821:virology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000821:virology; D008010:Lichen Planus / Q000453:epidemiology / Q000821:virology; D016393:Lymphoma, B-Cell / Q000453:epidemiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D017119:Porphyria Cutanea Tarda / Q000453:epidemiology / Q000821:virology; D015995:Prevalence; D011788:Quality of Life; D012859:Sjogren's Syndrome / Q000453:epidemiology / Q000821:virology
keywords: Liver; Morbidity; Outcome; Pancreatic