Document Type



Life Sciences | Medicine and Health Sciences


Background and Aims

Studies of the prognostic value of Ishak fibrosis stage are lacking. We utilized 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 biopsies from 1,050 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 pre-specified clinical outcomes of hepatic decompensation and hepatocellular carcinoma across individual Ishak fibrosis stages.


Of 1,050 biopsies 25% were fragmented, 63% >1.5 cm, 69% >10 mm2, and 75% had ≥10 portal tracts. Baseline laboratory markers of liver disease severity were worse and the frequency of esophageal varices higher with increasing Ishak stage (p<.0001). The six-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 non-fragmented biopsies, the predictive ability of Ishak staging was enhanced; however, no association was observed between Ishak stage and outcomes for fragmented biopsies due to high rates of outcomes for patients with non-cirrhotic stages. Similar results were observed with liver transplantation or liver-related death as the outcome.


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


Hepatology. Author manuscript; available in PMC 2013 October 31. Published in final edited form as: Hepatology. 2010 February; 51(2): 10.1002/hep.23315. doi: 10.1002/hep.23315 PMCID: PMC3814134 NIHMSID: NIHMS502635