Reduction in Hepatic Inflammation Is Associated With Less Fibrosis Progression and Fewer Clinical Outcomes in Advanced Hepatitis C
Year: 2012
Type: article
Abstract: OBJECTIVES: During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation. METHODS: Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological change was defined as a ≥ 2-point difference in HAI or Ishak fibrosis score between biopsies. RESULTS: Among 657 patients who received full-dose peginterferon/ribavirin "lead-in" therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both the randomized treated (P<0.0001) and control (P=0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both the treated (P=0.001) and control (P=0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared with those without such improvement in both the treated (P=0.03) and control (P=0.05) groups. Among patients with Ishak 3-4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both the treated (P=0.0003) and control (P=0.02) groups. CONCLUSIONS: Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment.
DOI: 10.1038/ajg.2012.137
Institutions: University of Washington, Bon Secours Health System, Harvard University, Massachusetts General Hospital, University of Southern California, University of Massachusetts Chan Medical School, University of Colorado Anschutz, University of Colorado Denver, University of Michigan, Michigan Medicine, Saint Louis University, National Institutes of Health, New England Research Institutes, University of California, Irvine, VA Long Beach Healthcare System, National Institute of Diabetes and Digestive and Kidney Diseases, Office of the Director
Language: English
Topic: Hepatitis C virus research
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1016094800, Hepatitis C Clinical Trials-Clinical Center, G1093595823, G1217208902, G1500039052, HEPATITIS C CLINICAL TRIAL-CLINICAL CENTERS, G1608726392, G1638345366, G1663837155, Hepatitis C Clinical Trial-Data Coordinating Center, G1740463284, G1789861183, GENERAL CLINICAL RESEARCH CENTER, G1952602728, G2095852620, G220748524, G2224345100, G2383253098, G239052087, G2605231874, Hepatitis C Clinical Trial-Clinical Center, Hepatitis C Clinical Trial-Clinical Center, G3277324657, G3350686849, Harvard Clinical and Translational Science Center (UL1), General Clinical Research Center, General Clinical Research Center, G3994153766, G417964966, G4310905822, Hepatitis C Clinical Trial-Clinical Center, G4627513917, G4749549782, G475936976, North and Central Texas Clinical and Translational Science Initiative (UL1), G5685827725, UT-Southwestern Clinical and Translational Alliance for Research (UT-STAR) (TL1), G57319417, General Clinical Research Center, General Clinical Research Center, Hepatitis C Clinical Trial-Clinical Center, G6062035232, G6063195862, HEPATITIS C CLINICAL TRIALS- CLINICAL CENTERS, G635792350, G645260498, HEPATITIS C CLINICAL TRIAL- CLINICAL CENTERS, G6793902845, Hepatitis C Clinical Trial-Clinical Center, G6998970483, G769717368, General Clinical Research Center, G838905924, G848270291, G8737339525, G881343144, General Clinical Research Center, G903953877, G937870883, Hepatitis C Clinical Trial-Clinical Center
OpenAlex ID: W2033765375