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Randomized Controlled Trial
. 2010 Feb;51(2):585-94.
doi: 10.1002/hep.23315.

Prognostic value of Ishak fibrosis stage: findings from the hepatitis C antiviral long-term treatment against cirrhosis trial

James E Everhart  1 , Elizabeth C Wright, Zachary D Goodman, Jules L Dienstag, John C Hoefs, David E Kleiner, Marc G Ghany, A Scott Mills, S Russell Nash, Sugantha Govindarajan, Thomas E Rogers, Joel K Greenson, Elizabeth M Brunt, Herbert L Bonkovsky, Chihiro Morishima, Heather J Litman; HALT-C Trial Group
Affiliations
Randomized Controlled Trial

Prognostic value of Ishak fibrosis stage: findings from the hepatitis C antiviral long-term treatment against cirrhosis trial

James E Everhart et al. Hepatology. 2010 Feb.

Abstract

Studies of the prognostic value of Ishak fibrosis stage are lacking. We used multi-year follow-up of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C. Baseline liver biopsy specimens from 1050 patients with compensated chronic hepatitis C who had failed combination peginterferon and ribavirin were reviewed by a panel of expert hepatopathologists. Fibrosis was staged with the Ishak scale (ranging from 0 = no fibrosis to 6 = cirrhosis). Biopsy fragmentation and length as well as number of portal tracts were recorded. We compared rates of prespecified clinical outcomes of hepatic decompensation and hepatocellular carcinoma across individual Ishak fibrosis stages. Of 1050 biopsy specimens, 25% were fragmented, 63% longer than 1.5 cm, 69% larger than 10 mm(2), and 75% had 10 or more portal tracts. Baseline laboratory markers of liver disease severity were worse and the frequency of esophageal varices higher with increasing Ishak stage (P < 0.0001). The 6-year cumulative incidence of first clinical outcome was 5.6% for stage 2, 16.1% for stage 3, 19.3% for stage 4, 37.8% for stage 5, and 49.3% for stage 6. Among nonfragmented biopsy specimens, the predictive ability of Ishak staging was enhanced; however, no association was observed between Ishak stage and outcomes for fragmented biopsy specimens because of high rates of outcomes for patients with noncirrhotic stages. Similar results were observed with liver transplantation or liver-related death as the outcome.

Conclusion: Ishak fibrosis stage predicts clinical outcomes, need for liver transplantation, and liver-related death in patients with chronic hepatitis C. Patients with fragmented biopsy specimens with low Ishak stage may be understaged histologically.

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Figures

Figure 1
Figure 1
Examples of fragmented biopsies. Specimen on left, which only has fibrosis focally along the edge of one fragment, was interpreted as Ishak stage 3. Specimen on right has fibrosis enveloping several fragments and was interpreted as Ishak stage 6.
Figure 2
Figure 2
Cumulative, 6-year incidence of first clinical liver disease outcome according to baseline Ishak fibrosis stage. a) all (non-fragmented and fragmented) biopsies, b) non-fragmented biopsies and c) fragmented biopsies.
Figure 3
Figure 3
Hazard rate ratios and 95% confidence intervals for clinical outcomes over 6 years for Ishak fibrosis stage relative to the next lower stage.
Figure 4
Figure 4
Cumulative incidence of transplantation or liver related death according to baseline Ishak fibrosis stage. a) all (non-fragmented and fragmented) biopsies, b) non-fragmented
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