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Randomized Controlled Trial
. 2011 Aug;54(2):396-405.
doi: 10.1002/hep.24370. Epub 2011 Jun 23.

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

Jules L Dienstag  1 , 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
Collaborators, Affiliations
Randomized Controlled Trial

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

Jules L Dienstag et al. Hepatology. 2011 Aug.

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.

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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
See this image and copyright information in PMC

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