Maintenance peginterferon therapy and other factors associated with hepatocellular carcinoma in patients with advanced hepatitis C.
OBJECTIVE
Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial showed that 4 years of maintenance therapy with pegylated interferon (peginterferon) does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer posttreatment follow-up period.


METHODS
The study included 1048 patients with chronic hepatitis C (Ishak fibrosis scores ≥ 3) who did not have a sustained virologic response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed up for a median of 6.1 (maximum, 8.7) years.


RESULTS
Eighty-eight patients developed HCC (68 definite, 20 presumed): 37 of 515 who were given peginterferon (7.2%) and 51 of 533 controls (9.6%; P = .24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.24-0.83); in treated and control patients with fibrosis, incidences were 8.3% and 6.8%, respectively (HR, 1.44; 95% CI, 0.77-2.69). Treated patients with a ≥ 2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs 9.4%; P = .03).


CONCLUSIONS
Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk of HCC than controls.
Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. aslok@umich.edu
Anna S
AS
Lok
James E
JE
Everhart
Elizabeth C
EC
Wright
Adrian M
AM
Di Bisceglie
Hae-Young
HY
Kim
Richard K
RK
Sterling
Gregory T
GT
Everson
Karen L
KL
Lindsay
William M
WM
Lee
Herbert L
HL
Bonkovsky
Jules L
JL
Dienstag
Marc G
MG
Ghany
Chihiro
C
Morishima
Timothy R
TR
Morgan
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a