title: The role of chronic norovirus infection in the enteropathy associated with common variable immunodeficiency.
abstract: OBJECTIVE
  A severe enteropathy of unknown etiology can be associated with common variable immunodeficiency (CVID).
  
  
  METHODS
  S tool and archived small intestinal mucosal biopsies from patients with CVID enteropathy were analyzed by PCR for the presence of Norovirus RNA. The PCR products were sequenced to determine the relationship of viral isolates. Stool samples from 10 patients with CVID but no enteropathy served as controls.
  
  
  RESULTS
  All eight patients in our CVID cohort with enteropathy showed persistent fecal excretion of Norovirus. Analysis of archived duodenal biopsies revealed a strong association between the presence of Norovirus and villous atrophy over a period of up to 8 years. Analysis of the viral isolates from each patient revealed distinct strains of genogroup II.4. Sequence analysis from consecutive biopsy specimens of one patient demonstrated persistence of the same viral strain over a 6-year period. CVID patients without enteropathy showed no evidence of Norovirus carriage. Viral clearance occurred spontaneously in one patient and followed oral Ribavirin therapy in two further patients, and resulted in complete symptomatic and histological recovery. However, Ribavirin treatment in two further patients was unsuccessful.
  
  
  CONCLUSIONS
  Norovirus is an important pathogen for patients with CVID and a cause of CVID enteropathy, as viral clearance, symptom resolution, and histological recovery coincide. Ribavirin requires further evaluation as a potential therapy.
authors.affiliation: Department of Gastroenterology and Clinical Nutrition, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Woodward
authors.affiliation: Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Effrossyni
authors.initials: E
authors.lastname: Gkrania-Klotsas
authors.affiliation: Public Health England, Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Anthony Yk
authors.initials: AY
authors.lastname: Cordero-Ng
authors.affiliation: Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Aloysious
authors.initials: A
authors.lastname: Aravinthan
authors.affiliation: Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Betty N
authors.initials: BN
authors.lastname: Bandoh
authors.affiliation: Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Davies
authors.affiliation: Public Health England, Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Clinical Biochemistry and Immunology, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Stevenson
authors.affiliation: Public Health England, Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Curran
authors.affiliation: Department of Clinical Biochemistry and Immunology, Cambridge University Hospitals NHS Foundation Trust and Cambridge University Medical School, Cambridge, UK.
authors.forename: Dinakantha
authors.initials: D
authors.lastname: Kumararatne
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D001706:Biopsy; D017250:Caliciviridae Infections / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D002908:Chronic Disease; D015331:Cohort Studies; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000473:pathology / Q000821:virology*; D004386:Duodenum / Q000473:pathology / Q000821:virology*; D005243:Feces / Q000821:virology; D005260:Female; D006801:Humans; D007410:Intestinal Diseases / Q000150:complications / Q000473:pathology / Q000821:virology*; D007421:Intestine, Small / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000235:genetics*; D012367:RNA, Viral / Q000032:analysis*; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin