A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C

Jules L Dienstag, Marc G Ghany, Timothy R Morgan, Adrian M Di Bisceglie, Herbert L Bonkovsky, Hae-Young Kim, Leonard B Seeff, Gyongyi Szabo, Elizabeth C Wright, Richard K Sterling, Gregory T Everson, Karen L Lindsay, William M Lee, Anna S Lok, Chihiro Morishima, Anne M Stoddard, James E Everhart, HALT-C Trial Group, Barbara F Banner, Maureen Cormier, Donna Giansiracusa, Gloria Borders, Michelle Kelley, Bruce Bacon, Brent Neuschwander-Tetri, Elizabeth M Brunt, Debra King, Raymond T Chung, Andrea E Reid, Atul K Bhan, Wallis A Molchen, David P Lundmark, Thomas Trouillot, Marcelo Kugelmas, S Russell Nash, Jennifer DeSanto, Carol McKinley, John C Hoefs, John R Craig, M Mazen Jamal, Muhammad Sheikh, Choon Park, Thomas E Rogers, Peter F Malet, Janel Shelton, Nicole Crowder, Rivka Elbein, Nancy Liston, Sugantha Govindarajan, Carol B Jones, Susan L Milstein, Robert J Fontana, Joel K Greenson, Pamela A Richtmyer, R Tess Bonham, Mitchell L Shiffman, Melissa J Contos, A Scott Mills, Charlotte Hofmann, Paula Smith, T Jake Liang, David Kleiner, Yoon Park, Elenita Rivera, Vanessa Haynes-Williams, Patricia R Robuck, Jay H Hoofmagle, David R Gretch, Minjun Chung Apodaca, Rohit Shankar, Natalia Antonov, Kristin K Snow, Margaret C Bell, Teresa M Curto, Zachary D Goodman, Fanny Monge, Michelle Parks, Gary L Davis, Guadalupe Garcia-Tsao, Michael Kutner, Stanley M Lemon, Robert P Perrillo, Jules L Dienstag, Marc G Ghany, Timothy R Morgan, Adrian M Di Bisceglie, Herbert L Bonkovsky, Hae-Young Kim, Leonard B Seeff, Gyongyi Szabo, Elizabeth C Wright, Richard K Sterling, Gregory T Everson, Karen L Lindsay, William M Lee, Anna S Lok, Chihiro Morishima, Anne M Stoddard, James E Everhart, HALT-C Trial Group, Barbara F Banner, Maureen Cormier, Donna Giansiracusa, Gloria Borders, Michelle Kelley, Bruce Bacon, Brent Neuschwander-Tetri, Elizabeth M Brunt, Debra King, Raymond T Chung, Andrea E Reid, Atul K Bhan, Wallis A Molchen, David P Lundmark, Thomas Trouillot, Marcelo Kugelmas, S Russell Nash, Jennifer DeSanto, Carol McKinley, John C Hoefs, John R Craig, M Mazen Jamal, Muhammad Sheikh, Choon Park, Thomas E Rogers, Peter F Malet, Janel Shelton, Nicole Crowder, Rivka Elbein, Nancy Liston, Sugantha Govindarajan, Carol B Jones, Susan L Milstein, Robert J Fontana, Joel K Greenson, Pamela A Richtmyer, R Tess Bonham, Mitchell L Shiffman, Melissa J Contos, A Scott Mills, Charlotte Hofmann, Paula Smith, T Jake Liang, David Kleiner, Yoon Park, Elenita Rivera, Vanessa Haynes-Williams, Patricia R Robuck, Jay H Hoofmagle, David R Gretch, Minjun Chung Apodaca, Rohit Shankar, Natalia Antonov, Kristin K Snow, Margaret C Bell, Teresa M Curto, Zachary D Goodman, Fanny Monge, Michelle Parks, Gary L Davis, Guadalupe Garcia-Tsao, Michael Kutner, Stanley M Lemon, Robert P Perrillo

Abstract

The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy-nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (P<0.0001). Child-Turcotte-Pugh (CTP) score≥7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score≥7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis.

Conclusion: Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7.

Trial registration: ClinicalTrials.gov NCT00006164.

Copyright © 2011 American Association for the Study of Liver Diseases.

Figures

Figure 1
Figure 1
First clinical outcome rates excluding death not related to liver by stratum and treatment group to year 8.
Figure 2
Figure 2
Cumulative 8-year incidence of all cause mortality, liver-related mortality and transplantation, and all cause mortality and liver transplantation: a) entire HALT-C Trial population, b) noncirrhotic advanced fibrosis and cirrhosis, c) CTP ≥7 on two consecutive visits, and d) after onset of decompensated liver disease.
Figure 2
Figure 2
Cumulative 8-year incidence of all cause mortality, liver-related mortality and transplantation, and all cause mortality and liver transplantation: a) entire HALT-C Trial population, b) noncirrhotic advanced fibrosis and cirrhosis, c) CTP ≥7 on two consecutive visits, and d) after onset of decompensated liver disease.
Figure 2
Figure 2
Cumulative 8-year incidence of all cause mortality, liver-related mortality and transplantation, and all cause mortality and liver transplantation: a) entire HALT-C Trial population, b) noncirrhotic advanced fibrosis and cirrhosis, c) CTP ≥7 on two consecutive visits, and d) after onset of decompensated liver disease.
Figure 2
Figure 2
Cumulative 8-year incidence of all cause mortality, liver-related mortality and transplantation, and all cause mortality and liver transplantation: a) entire HALT-C Trial population, b) noncirrhotic advanced fibrosis and cirrhosis, c) CTP ≥7 on two consecutive visits, and d) after onset of decompensated liver disease.
Figure 3
Figure 3
Cumulative incidence of laboratory abnormalities over time in a) the fibrosis stratum and b) the cirrhosis stratum

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir