SUMMARY: Obesity, fatty liver, and having hard-to-treat hepatitis C virus (HCV) genotype 1 predicted a greater likelihood of relapse after treatment, and thus failure to achieve sustained virological response, according to a French study presented at the recent American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) in Boston. Among women, however, the only independent predictor was being menopausal.

By Liz Highleyman

Christiane Stern and colleagues from Beaujon Hospital in Clichy, France, evaluated factors associated with post-treatment relapse among chronic hepatitis C patients -- particularly women -- treated with pegylated interferon plus ribavirin.

Response to hepatitis C treatment is typically assessed at week 4 (rapid virological response, or RVR), week 12 (early virological response, or EVR), the end of treatment, and then 24 weeks after completing treatment to ensure that HCV viral load remains undetectable (sustained virological response, or SVR). A significant number of patients relapse after finishing therapy.

A total of 249 previously untreated chronic hepatitis C patients were given pegylated interferon alfa-2a (Pegasys) or pegylated interferon alfa-2b (PegIntron) -- about half each -- plus 800-1200 mg/day weight-adjusted ribavirin. Patients with HCV genotypes 2 or 3 were treated for 24 weeks, while those with genotypes 1 or 4 were treated for 48 weeks.

The participants' average age was 47 years and 10% were classified as obese. About one-third were women, of whom 59% were menopausal (started at age 48, on average). One third had HCV genotype 1, 24% had advanced liver fibrosis (stage F3 or higher), and 27% had marked steatosis, or fat accumulation in liver cells.

Results

	34% of participants experienced HCV relapse after the end of treatment.
	In the study population as a whole, factors significantly associated with relapse in a logistic regression analysis were:
	Obesity; HCV genotype 1; Marked steatosis; Pegylated interferon dose reduction.
	To assess the influence of menopause on relapse in women, the investigators compared patients older and younger than 50 years according to sex.
	Among 165 men, 22% of those younger than 50 years and 25% of those older that 50 experienced relapse, not a significant difference.
	Among 84 women, however, 14% of those under age 50 and 37% of those above 50 years experienced relapse, which did reach statistical significance.
	Among women, factors significantly associated with relapse in a univariate analysis were menopause, obesity, high baseline viral load, HCV genotype 1, and moderate-to-severe liver necro-inflammation (stage A2 or higher).
	In a logistic regression analysis accounting for multiple factors, however, only menopause was independently associated with relapse.

Based on these findings, the investigators concluded, "Chronic hepatitis C patients infected with genotype 1 and presenting obesity and marked steatosis have higher rates of relapse."

"[Pegylated interferon] reduction, but not ribavirin reduction, is associated with relapse," they continued. "In female patients, menopause has a negative impact on SVR rates."

Prior research has tended to find that older patients on average to do respond as well to treatment as younger individuals. But in may cases such analyses did not take sex into account. The fact that this analysis saw an age difference for women but not men adds to the evidence that estrogen levels play a role in hepatitis C outcomes.

Investigator affiliation: Service d'Hépatologie, Hôpital Beaujon, Clichy, France.

12/10/10

Reference
C Stern, M Martinot-Peignoux, M Ripault, and other. Menopause is Associated with Relapse in Chronic Hepatitis C Patients Treated with Pegylated Interferon Plus Ribavirin. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 969.