The response to interferon treatment for patients with The present study was conducted to evaluate the relationship between biochemical, virological, and histological re-chronic hepatitis C was originally defined biochemically as a decline in the value of an elevated serum alanine amino-sponse during the course of interferon therapy. Ninety consecutive patients with well-documented chronic hepatitis C virus transferase (ALT) concentration into the normal range at the completion of therapy. According to this definition, 33%-(HCV) were treated with 5 MU of interferon alfa-2b three times weekly for 6 months. Liver biopsy was performed, and 50% of patients achieve biochemical response during treatment. [1][2][3][4][5][6][7] More recently, it has been shown that 80%-90% of serum HCV RNA titer was measured before and at the completion of interferon treatment. Normalization of serum alanine patients who achieve biochemical response also have virological response, i.e., disappearance of hepatitis C virus (HCV) transaminase (ALT) concentration (biochemical response) was observed in 50% of patients. In these patients, Knodell RNA from serum as assessed by a polymerase chain reaction (PCR) assay. [5][6][7][8] Unfortunately, approximately half of all pa-score declined significantly from 9.6 { 0.5 to 5.0 { 0.5 (P Γ΅ .01), and 75% became HCV RNA negative. The re-tients treated with interferon continue to be classified as nonresponders; serum ALT concentration remains elevated maining patients (50%) were biochemical nonresponders; mean Knodell score declined from 9.6 { 0.5 to 7.7 { 0.5 and HCV RNA remains detectable in serum throughout the duration of therapy. (P Γ΅ .01), and 11% became HCV RNA negative. For both biochemical responders and nonresponders, the decline in Biochemical and virological response to interferon therapy is associated with a significant improvement in hepatic histol-Knodell score was confined to the components of hepatic inflammation (piecemeal necrosis / lobular / portal inflam-ogy. [1][2][3][4][5][6][7] However, a consistent finding in many prior studies was that the mean hepatic histological index of interferon mation); no change in fibrosis was observed. Hepatic inflammation declined by 5 points or more in 69% of biochemical nonresponders also improved. We have therefore hypothesized that a subset of patients who do not respond to inter-responders and 48% of biochemical nonresponders, and by at least 50% from pretreatment values in 74% and 38% of feron, according to the classic definitions, may in fact have significant improvement in hepatic histology and thereby biochemical responders and biochemical nonresponders, respectively. For all patients (both biochemical responders and also benefit from interferon treatment.
The present study was performed to assess the relationship nonresponders) who remained viremic at the conclusion of interferon therapy, the reduction in hepatic inflammation was between biochemical, virological, and histological responses to interferon therapy in patients with chronic hepatitis C. a linear function of the decline in HCV RNA titer. We conclude that more than one third of patients who had no bio-Our results clearly document that more than one third of biochemical nonresponders do have histological improve-chemical response after 6 months of interferon therapy achieved a similar improvement in hepatic histology as was ment during interferon therapy and that this is typically associated with a decline in HCV RNA titer. The significance observed in patients with biochemical response. This improvement in hepatic histology appeared to correlate with a that these findings may have for the development of new treatment strategies for patients with chronic hepatitis C is reduction in HCV RNA titer, especially in patients who remained viremic. (HEPATOLOGY 1997;26:780-785.) discussed.