Virological and Histological Responses to One Year Alpha-Interferon-2a in Hemodialyzed Patients with Chronic Hepatitis C

Abstract

Background: α-Interferon-2a (IFNα) alone is a therapy of limited proven benefit for non-uremic patients with chronic hepatitis C virus (HCV) infection. In dialyzed patients, such an effect is suggested on small short-term studies without sufficient clinical and virologic follow-up to document any sustained effect. Protocol: Twelve chronically hemodialyzed patients with chronic hepatitis C and waiting for renal transplantation were included in a prospective open study of treatment with IFNα. We used, as did others, doses of 3 million units (MU), three times a week, but for a longer period of treatment of 12 months. Follow-up was continued for 6 months after the end of IFNα in order to document any sustained biochemical, virological and histological responses. Results: Aminotransferase levels returned to the normal range within 1–2 months of treatment in all patients in whom they had been elevated at baseline. At 1 month of treatment, serum HCV-RNA was not detected in 5 (41%) patients and in 9 (75%) at 12 months. A sustained virological response was documented in 4 (33%) patients 6 months after the end of treatment. Relapse occurred in 5 patients within 2 months after IFNα withdrawal. HCV genotype was not predictive of any sustained response. At inclusion, using the histologic Metavir scoring system, half of the patients had low-grade cytolytic activity and none had cirrhosis. After IFNα, liver biopsy specimens were available from 9 patients and showed histologic improvement in 3. IFNα tolerance was poor, inducing a 5% mean weight loss and the acute rejection of two nonfunctioning kidney grafts. Conclusion: This study documents that administration of IFNα at 3 MU three times a week, for 12 months, in hemodialysis patients with chronic hepatitis C was efficient for clearing the serum of HCV-RNA in 75% of the patients. A sustained response was maintained in one third of these patients after cessation of IFNα, and was predicted by the early serum clearance of the virus within the first 2 months of treatment. We confirm that a 12-month treatment period carries a higher sustained response rate than shorter treatment periods. These encouraging results call for larger studies in uremic patients, using IFNα alone or in association with new antiviral drugs.

Evidence that Clearance of Hepatitis C Virus RNA after α-Interferon Therapy in Dialysis Patients Is Sustained after Renal Transplantation

“…Rostaing et al (10) reported that the area under the curve of IFN-␣ is twice as high in hemodialysis patients compared with patients with normal renal function. This might explain why, according to previous reports (5,(11)(12)(13)(14), our patients had a mild tolerance of IFN-␣ compared with nonhemodialysis HCV-positive patients.…”

Meta‐analysis: interferon for the treatment of chronic hepatitis C in dialysis patients

“…In other words, these studies may not be measuring the same underlying quantity from the same base population. The summary estimates may not Chan TM, et al [43] Campistol J.M, et al [48] Hanrotel C, et al [52] Espinosa M, et al [49] Huraib S, et al [51] Fernandez J.L, et al [41] Mean overall estimate Koenig P, et al [33] Izopet J, et al [42] Casanovas-Taltavull T, et al…”

“…Uchihara M, et al [44] Benci A, et al [45] Chan T.M, et al [43] Izopet J, et al [42] Campistol J.M, et al [48] Hanrotel C, et al [52] Espinosa M, et al [49] Fernandez J.L, et al [41] Huraib S, et al [51] Mean overall estimate Koenig P, et al [33] Casanovas-Taltavull T, et al [50] Raptopoulou-Gigi M, et al [39] Pol S, et al [38] Degos F, et al [53] Patients discontinued treatment (%) -10% 10% 20% 30% 40% 50% 60% 70% 80% 90% 0% be the best descriptive analysis, since they assume that all estimates from individual studies are from the same population. The sources of between study heterogeneity are unclear.…”

Histologic outcomes in hepatitis C-infected patients with varying degrees of virologic response to interferon-based treatments

“…[8][9][10][11] Histologic response has also been observed in non-SVR patients who are coinfected with HCV/human immunodeficiency virus (HIV), 1,4,6,7 patients with advanced fibrosis or compensated cirrhosis, 2,3 and hemodialyzed patients with CHC. 12 Some of these studies also suggested that histologic improvements occurred in patients who became HCV RNA detectable following initial viral clearance (patients with relapse and breakthrough). 2,4 However, the number of patients with paired-biopsies in these individual studies was small.…”