BACKGROUND & AIMS: It is unclear whether surrogate end points reported in clinical trials correlate with long-term outcome of patients with chronic hepatitis B. METHODS:Patients with chronic hepatitis B who participated in any of 4 randomized controlled trials were followed prospectively for liver-related events (hepatocellular carcinoma, ascites, spontaneous bacterial peritonitis, variceal bleeding, liver transplantation, and death). Biochemical (normal ALT levels), virologic (levels of hepatitis B virus DNA below 10,000 copies/mL), and histologic (reduction of necroinflammation grading by 2 points or more with no increase in fibrosis staging) responses were evaluated at the end of each trial. RESULTS:One hundred ninety-five patients with adequate pretreatment and post-treatment liver biopsies (15 mm long and 6 portal tracts) were followed for 86 months (interquartile range, 77-98). Liver-related events occurred in 12 patients (6%). The risk of liver-related events was lower in patients with biochemical (hazard ratio, 0.21; 95% confidence interval, 0.068-0.68) and histologic (hazard ratio, 0.095; 95% confidence interval, 0.012-0.74) responses. Only 1 patient with a histologic response and 1 patient with an ALT level below Prati's cutoffs (30 IU/L in men and 19 IU/L in women) developed liver-related events. Fifteen of 25 patients (60%) with cirrhosis at baseline had regression of cirrhosis, and none of these patients died or developed liver-related events. In contrast, 3 of these patients still developed liver-related events, despite an initial virologic response, and 2 had virologic breakthrough. CONCLUSIONS:Biochemical and histologic responses, particularly regression of cirrhosis, in patients with chronic hepatitis B are associated with decreased liver-related complications.
RCT Entities:
BACKGROUND & AIMS: It is unclear whether surrogate end points reported in clinical trials correlate with long-term outcome of patients with chronic hepatitis B. METHODS:Patients with chronic hepatitis B who participated in any of 4 randomized controlled trials were followed prospectively for liver-related events (hepatocellular carcinoma, ascites, spontaneous bacterial peritonitis, variceal bleeding, liver transplantation, and death). Biochemical (normal ALT levels), virologic (levels of hepatitis B virus DNA below 10,000 copies/mL), and histologic (reduction of necroinflammation grading by 2 points or more with no increase in fibrosis staging) responses were evaluated at the end of each trial. RESULTS: One hundred ninety-five patients with adequate pretreatment and post-treatment liver biopsies (15 mm long and 6 portal tracts) were followed for 86 months (interquartile range, 77-98). Liver-related events occurred in 12 patients (6%). The risk of liver-related events was lower in patients with biochemical (hazard ratio, 0.21; 95% confidence interval, 0.068-0.68) and histologic (hazard ratio, 0.095; 95% confidence interval, 0.012-0.74) responses. Only 1 patient with a histologic response and 1 patient with an ALT level below Prati's cutoffs (30 IU/L in men and 19 IU/L in women) developed liver-related events. Fifteen of 25 patients (60%) with cirrhosis at baseline had regression of cirrhosis, and none of these patients died or developed liver-related events. In contrast, 3 of these patients still developed liver-related events, despite an initial virologic response, and 2 had virologic breakthrough. CONCLUSIONS: Biochemical and histologic responses, particularly regression of cirrhosis, in patients with chronic hepatitis B are associated with decreased liver-related complications.
Authors: Vincent Wai-Sun Wong; Grace Lai-Hung Wong; Chi-Hang Tse; Lilly K W Yuen; Hoi-Yun Chan; Stephen A Locarnini; Henry Lik-Yuen Chan Journal: Dig Dis Sci Date: 2011-07-09 Impact factor: 3.199
Authors: Willem P Brouwer; Henry L Y Chan; Pietro Lampertico; Jinlin Hou; Pisit Tangkijvanich; Hendrik W Reesink; Wenhong Zhang; Alessandra Mangia; Tawesak Tanwandee; Giuseppe Montalto; Kris Simon; Necati Ormeci; Liang Chen; Fehmi Tabak; Fulya Gunsar; Robert Flisiak; Peter Ferenci; Meral Akdogan; Filiz Akyuz; Nattiya Hirankarn; Louis Jansen; Vincent Wai-Sun Wong; Roberta Soffredini; Xieer Liang; Shalom Chen; Zwier M A Groothuismink; Rosanna Santoro; Jerzy Jaroszewicz; Resat Ozaras; Karin Kozbial; Mayur Brahmania; Qing Xie; Watcharasak Chotiyaputta; Qi Xun; Monika Pazgan-Simon; Erkin Oztas; Elke Verhey; Noé R Montanari; Jian Sun; Bettina E Hansen; Andre Boonstra; Harry L A Janssen Journal: Clin Infect Dis Date: 2019-11-13 Impact factor: 9.079