title: A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C.
abstract: The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy-nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (P<0.0001). Child-Turcotte-Pugh (CTP) score≥7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score≥7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis.
  
  
  CONCLUSIONS
  Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7.
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, MA 02114, USA. jdienstag@partners.org
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Seeff
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Szabo
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.forename: Karen L
authors.initials: KL
authors.lastname: Lindsay
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Anna S
authors.initials: AS
authors.lastname: Lok
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stoddard
authors.forename: James E
authors.initials: JE
authors.lastname: Everhart
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a