Szabo G, Banner BF, Cormier M, Giansiracusa D, Kelley M, Bacon B, Neuschwander-Tetri B, Brunt EM, King D, Chung RT, Reid AE, Bhan AK, Molchen WA, Nash SR, Kugelmas M, DeSanto J, McKinley C, Hoefs JC, Craig JR, Sheik M, Jamal MM, Park C, Rogers TE, Malet PF, Shelton J, Crowder N, Elbein R, Govindarajan S, Jones CB, Milstein SL, Fontana RJ, Greenson JK, Richtmyer PA, Sterling RK, Contos MJ, Mills AS, Hofmann C, Smith P, Liang TJ, Kleiner D, Park Y, Rivera E, Haynes-Williams V, Seeff LB, Robuck PR, Hoofnagle JH, Gretch DR, Chung M, Shankar R, Bell MC, Stoddard AM, Curto TM, Massey LJ, Mihova MS, Naishadham D, Padmanabhan L, Tran D, Chen FY, Goodman ZD, Davis GL, Garcia-Tsao G, Kutner M, Lemon SM, Perrillo RP.
Source
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
Abstract
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.)
2008 Massachusetts Medical Society