Failure to respond to interferon-α 2a therapy is associated with increased hepatic iron levels in patients with chronic hepatitis C

Abstract

Recent reports suggest the hepatic iron concentration (HIC) may influence the activity of hepatitis and the response to interferon (IFN) therapy in patients with chronic hepatitis C (CH-C). We have evaluated iron status in 28 patients with CH-C and determined if pretreatment iron status can predict the response to IFN-alpha therapy in these patients. Increased serum iron, transferrin saturation, and ferritin levels were observed in 3 (11%), 11 (39%), and 5 (18%) patients, respectively. Hepatic iron deposits were histologically detected in 17 (61%) patients, and 14 of them had stainable hepatocytic iron. However, all HIC values were within the normal range (203-1279 microg/g). Seven of 17 patients treated with IFN-alpha for 6 mo had normalization of serum transaminases and disappearance of serum HCV-RNA (responders). Nonresponders had a significantly higher median HIC compared with responders (710 vs 343 microg/g, respectively; p < 0.05). There was no significant difference in other pretreatment iron parameters, serum HCV-RNA level, or HCV-genotype between responders and nonresponders. In conclusion, mild hepatic iron accumulation occurs in patients with CH-C. Increased hepatic iron stores are associated with poor response to IFN therapy. Pretreatment HIC may be an additional host-specific parameter with a predictive value for responsiveness to IFN therapy, in addition to well-known predictive viral factors.

Racial differences in the relationship between hepatitis C infection and iron stores

“…On the other hand, the fact that iron depletion by phlebotomy in patients with HCV reduces serum aminotransferase levels [38][39][40][41][42][43] and, in combination with interferon, may have improved antiviral efficacy compared with interferon alone 39,41,43 suggests that increased iron stores may be the cause of the reduced response to interferon. Although the presence of increased iron stores is a recognized predictor of poor response to interferon monotherapy, [15][16][17][18][19][20][21][22] the association between increased iron stores and response to combination treatment with interferon and ribavirin or pegylated interferon and ribavirin has not been investigated adequately. Only one such study is currently available 44 in which 40 patients were treated with interferon and ribavirin, of whom 18 had sustained virologic response.…”

“…[7][8][9][10][11][12][13] The presence of elevated body iron stores and, in particular, elevated hepatic iron levels, is one of the strongest predictors of resistance to interferon treatment for HCV. [14][15][16][17][18][19][20][21][22] We used data from the third National Health and Nutrition Examination Survey (NHANES III) to determine whether there are differences between HCV-infected blacks and HCV-infected nonblacks with respect to the likelihood of increased iron stores. We hypothesized that among persons with HCV infection, a greater percentage of blacks than nonblacks would have elevated iron stores, because such a finding would be in agreement with the observed lower response of blacks to antiviral treatment.…”

Effect of iron overload on the severity of liver histologic alterations and on the response to interferon and ribavirin therapy of patients with hepatitis C infection

“…Some researchers considered iron overload to be a factor contributing to a decreased response to treatment (16,17). Later investigations reported contradictory results.…”

Treatment of chronic hepatitis C in nonresponders to interferon monotherapy

“…A study from Japan evaluated the iron status of 28 patients with chronic hepatitis C who were treated with interferon [1]. Hepatic iron deposits were detected in 17 of 28 liver biopsies of patients treated with interferon alfa.…”