Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon.
BACKGROUND
In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain.


METHODS
We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 microg per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of fibrosis (622 with noncirrhotic fibrosis and 428 with cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points.


RESULTS
We randomly assigned the patients to receive peginterferon (517 patients) or no therapy (533 patients) for 3.5 years. The level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly (P<0.001) with treatment, but there was no significant difference between the groups in the rate of any primary outcome (34.1% in the treatment group and 33.8% in the control group; hazard ratio, 1.01; 95% confidence interval, 0.81 to 1.27; P=0.90). The percentage of patients with at least one serious adverse event was 38.6% in the treatment group and 31.8% in the control group (P=0.07).


CONCLUSIONS
Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who had not had a response to initial treatment with peginterferon and ribavirin. (ClinicalTrials.gov number, NCT00006164.)
Di Bisceglie
Adrian M
AM
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, 3635 Vista Ave., St. Louis, MO 63110, USA. dibiscam@slu.edu
Shiffman
Mitchell L
ML
Everson
Gregory T
GT
Lindsay
Karen L
KL
Everhart
James E
JE
Wright
Elizabeth C
EC
Lee
William M
WM
Lok
Anna S
AS
Bonkovsky
Herbert L
HL
Morgan
Timothy R
TR
Ghany
Marc G
MG
Morishima
Chihiro
C
Snow
Kristin K
KK
Dienstag
Jules L
JL
D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D000410:Alanine Transaminase