title: Long-Term Prognostic Significance of Persisting Histological Activity Despite Biochemical Remission in Autoimmune Hepatitis.
abstract: OBJECTIVE
  Biochemical remission is widely considered a satisfactory treatment end point in autoimmune hepatitis (AIH). The significance of persisting histological activity despite biochemical remission is unknown. We aimed to assess the frequency and prognostic significance of persisting histological inflammation in patients with AIH who had achieved biochemical remission with treatment.
  
  
  METHODS
  We studied 120 patients (median age at diagnosis 57 years; 81% female) with AIH by International Criteria (59% definite), who received immunosuppressive treatment and underwent a follow-up liver biopsy after at least 6 months of sustained biochemical remission (defined as normal serum ALT and globulin).
  
  
  RESULTS
  Fifty-five patients (46%) had persisting histological activity (Ishak histological activity index (HAI) ≥4). These patients had higher serum ALT (24 vs. 18 IU/l, P=0.003) and AST (27 vs. 23 IU/l, P=0.03) at the time of follow-up biopsy, compared with patients who achieved histological remission (HAI ≤3). They had less frequent regression of fibrosis on follow-up biopsy compared with those achieving histological remission (32 vs. 60%, P=0.004) and had excess mortality (standardized mortality ratio 1.4 vs. 0.7, P<0.05). The excess mortality was due to liver disease. On multivariate analysis, persisting histological activity was independently associated with all-cause death/transplantation (HR 3.1 (95% CI 1.2-8.1); P=0.02); an association with liver-related death/transplantation fell short of significance (HR 9.7 (95% CI 0.84-111.6; P=0.07).
  
  
  CONCLUSIONS
  Persisting histological activity, despite biochemical remission, is frequent in patients with treated AIH and is associated with lower rates of fibrosis regression and reduced long-term survival.
authors.affiliation: Liver Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK.
authors.forename: Harpreet K
authors.initials: HK
authors.lastname: Dhaliwal
authors.affiliation: Department of Gastroenterology, Rotherham General Hospital, Rotherham, UK.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Hoeroldt
authors.affiliation: Department of Histopathology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors.forename: Asha K
authors.initials: AK
authors.lastname: Dube
authors.affiliation: Liver Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: McFarlane
authors.affiliation: Academic Unit of Pathology, University of Sheffield, Sheffield, UK.
authors.forename: James C E
authors.initials: JC
authors.lastname: Underwood
authors.affiliation: Liver Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Karajeh
authors.affiliation: Liver Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK.
authors.forename: Dermot
authors.initials: D
authors.lastname: Gleeson
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D007166:Immunosuppressive Agents; D011239:Prednisolone; D009173:Mycophenolic Acid; D001379:Azathioprine