Pallavi Surana1, Devika Kapuria1, Carly Broadwell1, Elizabeth C Wright2, Varun Takyar1, David E Kleiner3, Marc G Ghany1, Gil Ben-Yakov1, Theo Heller1, T Jake Liang1, Christopher Koh4. 1. Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. 2. Office of the Director, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. 3. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 4. Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: Christopher.koh@nih.gov.
Abstract
BACKGROUND: Fibrosis regression has been associated with nucleoside analogue (NA) treatment in chronic hepatitis B (CHB) patients. Although non-invasive fibrosis markers have been evaluated in CHB, their utility for monitoring on-treatment histologic regression has not been evaluated. AIMS: To characterize improvements in disease severity and the utility of non-invasive biomarkers in CHB NA treated patients. METHODS: Histology, labs, AST-to-platelet ratio index, and Fibrosis-4 (Fib-4) from treatment-naïve CHB patients were evaluated at baseline and longitudinally. Relative change from baseline to various time points during treatment were evaluated. Correlative analysis of APRI and Fib-4 with histology was performed longitudinally. RESULTS: 80 CHB patients (84% male, median age 45 (IQR 32, 54)) with histology up to 17 years (median 6(IQR 3.9, 8.0)) years were studied. Median baseline Ishak fibrosis was 3 (IQR 2, 4), histologic activity index (HAI) inflammation was 9 (IQR 7, 11), and AUROC of fibrosis markers for detecting cirrhosis (Ishak ≥ 5) was >0.64. HAI improved at a rate of 54% during year 1 and 37% in year 2, both greater than in the remaining follow-up periods. Within the first year, fibrosis improved by 35%, greater than all other time periods. Non-invasive biomarkers began to correlate with histology beyond 4 years (APRI: 4-6 years: r = 0.33, p = 0.03; ≥6 years: r = 0.41, p = 0.009; Fib-4: ≥6 years: r = 0.35, p = 0.03). CONCLUSION: Early dynamic changes in histology occur in CHB patients on NA followed by linear improvements. Non-invasive fibrosis biomarkers do not capture these dynamic changes and may demonstrate clinical utility beyond 4 years of treatment. Published by Elsevier B.V.
BACKGROUND:Fibrosis regression has been associated with nucleoside analogue (NA) treatment in chronic hepatitis B (CHB) patients. Although non-invasive fibrosis markers have been evaluated in CHB, their utility for monitoring on-treatment histologic regression has not been evaluated. AIMS: To characterize improvements in disease severity and the utility of non-invasive biomarkers in CHB NA treated patients. METHODS: Histology, labs, AST-to-platelet ratio index, and Fibrosis-4 (Fib-4) from treatment-naïve CHB patients were evaluated at baseline and longitudinally. Relative change from baseline to various time points during treatment were evaluated. Correlative analysis of APRI and Fib-4 with histology was performed longitudinally. RESULTS: 80 CHB patients (84% male, median age 45 (IQR 32, 54)) with histology up to 17 years (median 6(IQR 3.9, 8.0)) years were studied. Median baseline Ishak fibrosis was 3 (IQR 2, 4), histologic activity index (HAI) inflammation was 9 (IQR 7, 11), and AUROC of fibrosis markers for detecting cirrhosis (Ishak ≥ 5) was >0.64. HAI improved at a rate of 54% during year 1 and 37% in year 2, both greater than in the remaining follow-up periods. Within the first year, fibrosis improved by 35%, greater than all other time periods. Non-invasive biomarkers began to correlate with histology beyond 4 years (APRI: 4-6 years: r = 0.33, p = 0.03; ≥6 years: r = 0.41, p = 0.009; Fib-4: ≥6 years: r = 0.35, p = 0.03). CONCLUSION: Early dynamic changes in histology occur in CHB patients on NA followed by linear improvements. Non-invasive fibrosis biomarkers do not capture these dynamic changes and may demonstrate clinical utility beyond 4 years of treatment. Published by Elsevier B.V.
Authors: Zobair M Younossi; Maria Stepanova; Issah Younossi; Calvin Q Pan; Harry L A Janssen; George Papatheodoridis; Fatema Nader Journal: Clin Gastroenterol Hepatol Date: 2018-09-27 Impact factor: 11.382
Authors: Zobair M Younossi; Maria Stepanova; Harry L A Janssen; Kosh Agarwal; Mindie H Nguyen; Ed Gane; Naoky Tsai; Issah Younossi; Andrei Racila Journal: Clin Gastroenterol Hepatol Date: 2018-03-02 Impact factor: 11.382
Authors: Seung Kak Shin; Jeong Han Kim; Hyeonsu Park; Oh Sang Kwon; Hyun Jung Lee; Jong Eun Yeon; Kwan Soo Byun; Sang Jun Suh; Hyung Joon Yim; Yun Soo Kim; Ju Hyun Kim Journal: J Gastroenterol Hepatol Date: 2015-12 Impact factor: 4.029
Authors: Patrick Marcellin; Ting-Tsung Chang; Seng Gee Lim; Myron J Tong; William Sievert; Mitchell L Shiffman; Lennox Jeffers; Zachary Goodman; Michael S Wulfsohn; Shelly Xiong; John Fry; Carol L Brosgart Journal: N Engl J Med Date: 2003-02-27 Impact factor: 91.245