Human leucocyte interferon-α in chronic hepatitis C resistant to recombinant or lymphoblastoid interferon-α: a randomized controlled trial

Patients with biopsy-proven chronic hepatitis C, who failed to respond to a previous course of either recombinant (rIFN-α) or lymphoblastoid (LyIFN-α) interferon-α, were randomized to receive either leucocyte (Le) IFN-α (patients) or a second course of the same IFN-α (controls), to compare the efficacy and safety of these treatment schedules. All patients received the same dose of IFN-α as was used during their previous treatment (3 million units (MU) or 6MU three times weekly) for 6 months. Patients with a normal alanine aminotransferase (ALT) value at month 6 were treated for a further 6 months. All patients were followed-up for 12 months after treatment. A total of 69 patients were enrolled, 44 in the LeIFN-α group and 25 in the control group. At the end of the treatment period, 13 of the 44 patients (29.5%) in the LeIFN-α group had a biochemical response (normal ALT) and six of 44 (13.6%) patients had undetectable serum hepatitis C virus (HCV) RNA. At the end of the follow-up period, 10 patients (22.7%) had normal ALT values and serum HCV RNA was undetectable in three (6.8%). None of the patients in the control group showed normal ALT values at any time. Genotype 1b tended to be more frequent among non-responders (61 vs 45%); basal γ-glutamyl transpeptidase (γ-GT) values were lower in responders than in non-responders (33.3±11.70 Ul^–1 vs 58.4±33.04; P =0.01). LeIFN-α was well tolerated by all patients. These results support the use of LeIFN-α in patients with chronic hepatitis C who are non-responders to a previous treatment with recombinant or lymphoblastoid IFN-α.     

Clinical efficacy of intramuscular human interferon-βvs interferon-α2b for the treatment of chronic hepatitis C

Summary. We have conducted a randomized study to compare the efficacy and tolerance of human interferon (IFN) β vs recombinant IFN-α2b in patients with chronic active hepatitis C. Forty patients were included: 21 received IFN-α (group A) and 19 IFN-β (group B). IFN was administered intramuscularly at a dose of 6 MU three times a week (tiw) for 2 months (induction phase), followed by 3 MU tiw for 4 months. Clinical, epidemiological and pathological features were similar in the two groups. Normal alanine aminotransferase (ALT) values at the end of treatment was regarded as a response to therapy and the response rate was 57% (12/21) in group A and 5.2% (1/19) in group B ( P < 0.01). Both types of IFN induced a significant decrease in mean ALT values by the end of the induction phase ( P < 0.01). When the dose was reduced to 3 MU, a marked, but not significant increase in ALT, was seen in group B, whereas no increase was seen in group A. IFN-β was better tolerated and haematological adverse effects (platelet and leucocyte decrease) were less pronounced with IFN-β. Hence, human IFN-β was less effective than IFN-α in treating chronic hepatitis C virus (HCV). Doses of IFN-β of 3 MU intramuscular (IM) tiw were clearly insufficient and it remains to be established whether higher doses of intramuscularly IFN-β can be useful.     

Interim analysis of a randomized controlled trial of combination of ribavirin and high dose interferon-α in interferon nonresponders with chronic hepatitis C

This trial investigated the efficacy of a combination of high-dose interferon-α (IFN-α) with ribavirin in IFN nonresponders. Study protocol: 304 patients with chronic hepatitis C were treated with 5 MU IFN-α2b (IntronA^®, Schering-Plough) per TIW for 3 months. Nonresponders (defined by HCV-RNA positivity in serum after the 3 months of therapy) were randomized either to continue with IFN (5 MU IFN per TIW followed by 10 MU per TIW for each 3 months) alone (group A) or in combination with ribavirin (1–1.2 g per day) (group B). ALT was measured in monthly intervals, HCV-RNA in 3 monthly intervals. Pretreatment characteristics of the randomized patients were as follows: group A, n = 76; m/f, 54/22; 16% cirrhosis, age, 45.7 ± 12 years; ALT (U per litre), 66 ± 35; group B, n = 81; m/f, 57/24; 17% cirrhosis, age, 48.2 ± 12; ALT, 71 ± 40. After 9 months of treatment, nine (11.6%) and 27 (32.5%, P = 0.0066) patients were HCV-RNA negative and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in group A and 15 in group B. Six months after treatment only two patients in group A (2.5%) and five (6%, P = 0.06) in group B had normal ALT and no detectable HCV-RNA in serum. In addition to the well-known side-effects of IFN the mean haemoglobin concentration dropped by 2 g per litre in group B. These data indicate that a combination of high-dose IFN with ribavirin is effective in inducing a short-lasting complete response in one-third of IFN nonresponders. Prolonged treatment with IFN/ribavirin may be necessary to obtain a sustained response.     

Long-term interferon-α treatment of children with chronic hepatitis delta: a multicentre study

Summary We assessed the efficacy of prolonged interferon-α (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-α2b(5 MU m^-2, then 3 MU m^-2 three times weekly for 12 (medium-term group, MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis Be antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-α treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.     

A short induction regimen of interferon-alpha is not effective for treatment of relapse in chronic hepatitis C: a randomized trial. For the multicentre GER-CYT-01 group

The aim of this work was to assess the effect of a high-dose (10 million units, MU) short-duration (14 weeks) interferon-α2b (IFN-α2b) regimen in relapsers compared with the standard IFN regimen of 3 MU three times weekly (t.i.w.) for 6 months. Fifty-eight non-cirrhotic patients (who had relapsed after previous treatment with IFN) with chronic hepatitis were randomized: 29 to the high-dose, short-duration regimen and 29 to the standard regimen. By the end of IFN therapy, in the high-dose, short-duration group alanine aminotransferase (ALT) normalization was observed in 23 (79%) of 29 patients, and undetectable hepatitis C virus (HCV) RNA in eight (28%) vs 25 (86%) and 11 (38%) of the 29 patients in the standard group, respectively ( P = NS). At the end of the 72-week follow-up, in the high-dose, short-duration group a sustained ALT normalization was observed in two (7%) patients, and undetectable HCV RNA in 0 (0%) vs five (17%) and four (14%) patients in the standard group ( P = NS). There was less fibrosis improvement in the high-dose, short-duration group (two of 26 patients, 8%) than in the standard group (eight of 25 patients, 32%) ( P = 0.04). Tolerance to IFN was good and similar in the two groups. In conclusion, in IFN relapsers, high-dose, short-duration treatment with IFN-α has no advantage when compared to a 6-month treatment with 3 MU IFN t.i.w.     

A randomized controlled trial of kurorinone versus interferon-alpha2a treatment in patients with chronic hepatitis B

It has recently been shown that a Chinese traditional medicine, kurorinone, extracted from Sophora Flavescens Ait, possesses antiviral properties. We evaluated the efficacy and safety of kurorinone treatment in patients with chronic hepatitis B. Ninety-four patients with abnormal alanine transaminase (ALT) levels and hepatitis B e antigen (HBeAg) and/or hepatitis B virus (HBV) DNA-positivity were randomly assigned to receive either kurorinone 400 mg daily (45 patients) or 3 million units (MU) of interferon-α (IFN-α) (49 patients, daily for 1 month, every other day for 2 months) for 3 months. Patients were followed-up for 12 months. At baseline, both groups were comparable regarding age, gender and serological parameters. At the end of treatment, complete response (defined as ALT normalization and HBeAg and/or HBV DNA loss) occurred in 50% of the kurorinone group and in 61.3% of the IFN-α-treated group ( P  > NS). At the end of the 12-month follow-up period, a complete response (sustained response) occurred in 26.7–36.7% of kurorinone-treated patients with moderate or mild liver damage and in 44.4–46.7% of IFN-α-treated patients with similar liver injury. In kurorinone- as well as in IFN-α-treated patients, there was no statistical significant difference with respect to complete response rates between HBeAg-positive and hepatitis B e antibody-positive subgroups. Kurorinone had no untoward side-effects except for local pain at injection sites. The results of this trial suggest that kurorinone is able to inhibit HBV replication and improve disease remission in patients with chronic hepatitis B.     

Hepatitis C virus RNA and long-term response to recombinant interferon-α2b in patients with chronic hepatitis C

Summary. The effectiveness of recombinant interferon-α2b (rIFN-α2b) in eradicating hepatitis C virus (HCV) RNA from serum has not been completely assessed. We studied 39 patients with compensated chronic hepatitis C diagnosed by liver biopsy and positive HCV RNA measured by polymerase chain reaction (PCR). Group I consisted of 26 patients treated with 3 MU of rIFN-α2b for 6 months; group II, 13 control patients observed for six months; and group III, 12 out of 13 patients from group n who subsequently received 5 MU of rIFN-α2b for 6 months. In group I, 11 out of 23 (47.8%) patients who completed treatment had an immediate response and five (21.7%) had a sustained response to therapy six months after treatment. No response was observed in patients from group II. In group III, 7 out of 12 (58.3%) patients who completed treatment had an immediate response and none had a sustained response. Considering all patients who completed rIFN-α2b treatment, HCV RNA remained positive at the end of therapy in three of five sustained responders (60%), six of 13 patients who relapsed (46.1%), and in all non-responders (100%). HCV RNA was positive 6 months after therapy in four (80%), 13 (100%). and 17 (100%) patients respectively. All patients with a sustained response had normal aminotransferase levels 18 months after therapy. We conclude that in chronic hepatitis C rIFN-α2b causes a significant immediate response but this is not sustained, only 2.8% of treated patients had a sustained loss of HCV RNA. Normal aminotransferase persist in the long term, despite persistence of HCV RNA.     

Interferon-α plus amantadine in chronic hepatitis C resistant to interferon alone: a pilot randomized study

The optimal therapy for patients with chronic hepatitis C who have not responded to interferon (IFN) is still an unsolved issue. The aim of this study was to evaluate the efficacy and tolerability of a high dose of IFN-α2a plus amantadine for chronic hepatitis C patients who were non-responders to a previous course of IFN.
Forty consecutive patients with chronic hepatitis C, genotype 1b, who had not responded to IFN-α, were randomized to receive: (i) IFN 4.5  M U daily plus amantadine 200 mg/day for 4 weeks and then IFN 6  M U thrice weekly plus amantadine 200 mg/day for an additional 5 months (group A) or (ii) IFN alone at the same dosage and duration (group B). After 1 month of therapy, normal alanine aminotransferase (ALT) values were observed in three of 21 (14.3%) patients in group A and in three of 19 (15.8%) in group B; serum hepatitis C virus (HCV)-RNA clearance was observed in one patient (4.8%) in group A and in six (31.6%) in group B. At the end of treatment, six patients (28.6%) in group A and three (15.8%) in group B had normal ALT levels; however, HCV-RNA in serum was detectable in all of them at levels comparable to the basal values; an ALT relapse occurred within 3 months of stopping therapy. The combination of daily IFN plus amantadine was ineffective in this setting.     

Interferon-α-2B and ribavirin in combination for chronic hepatitis C patients not responding to interferon-α alone: an italian multicenter, randomized, controlled, clinical study

Objective: The aim of the study was to assess the efficacy of interferon (IFN)-α-2b and ribavirin in combination in the treatment of chronic hepatitis C (CHC) patients unresponsive to a previous treatment with IFN-α−2b alone.
Methods: We conducted a randomized study in 303 CHC patients. One hundred fifty-two patients received subcutaneous administration of recombinant IFN-α−2b (3 MU thrice weekly) and ribavirin (1000–1200 mg/daily per os ), whereas 151 received IFN-α−2b alone (6 MU thrice weekly). Both ribavirin and IFN-α-2b were given for 24 wk, regardless of treatment response. Alanine aminotransferase (ALT) levels and HCV RNA titer were checked during the treatment period and for a further 24 wk.
Results: Normal ALT levels were observed in 64.5% of the patients treated with IFN-α and ribavirin and in 22.6% of the patients treated with IFN-α alone. In the group of patients receiving IFN-α and ribavirin HCV RNA was not detectable in 40% of patients responders and remained undetectable in 44.2% of sustained responders. In the group of patients receiving IFN-α alone HCV RNA was not detectable in 24.2% of patients responders and remained not detectable in 33.3% of sustained responders.
Conclusion: A 24-wk treatment course with IFN-α and ribavirin given to patients with a previous lack of response to IFN-α alone offers a chance of a sustained biochemical and virological response, at least in a subset of such patients. The role of long-term therapy in inducing prolonged remission still remains to be explored.     

Expression of interferon-alpha subtypes in peripheral mononuclear cells from patients with chronic hepatitis C: a role for interferon-alpha5

Interferon (IFN)-α is a family of antiviral proteins encoded by different genes. The biological significance of the existence of various IFN-α subtypes is not clear. We have investigated the interferon system in chronic hepatitis C virus (HCV) infection, a disease that responds to interferon-α2 therapy in only a limited proportion of cases. We analysed the expression of interferon regulatory factor (IRF)-1, IRF-2, and IFN-α subtypes in nonstimulated and Sendai virus-stimulated peripheral blood mononuclear cells (PBMC) from HCV infected patients and healthy controls. We observed that the IRF-1 mRNA and IRF-1/IRF-2 ratios were increased in PBMC from hepatitis C patients with respect to normal subjects. Sendai virus stimulation of PBMC led to a significant increase in the levels of IRF-1, IRF-2 and IFN-α mRNAs and in the production of IFN-α protein with respect to basal values in healthy controls as well as in patients with HCV infection. In addition, we found that while natural HCV infection induced increased IFN-α5 expression in PBMC, in vitro infection of these cells with Sendai virus caused a raise in the expression of IFN-α8 in both patients and normal controls. In summary, our results indicate that virus-induced activation of the IFN system in human PBMC is associated with selective expression of individual IFN-α subtypes, IFN-α5 being the specific subtype induced in PBMC from patients with chronic HCV infection.     

Comparison of thrice weekly vs daily human leucocyte interferon-alpha therapy for chronic hepatitis C. TVVH Study Group

Standard treatment for chronic hepatitis C currently consists of 3–6 million units (MU) of interferon-α (IFN-α) given thrice weekly (t.i.w.) for 12 months, obtaining rates of sustained response (SR) that usually do not exceed 15–25%. Some recent reports have suggested that daily administration of IFN-α may be more efficacious. More than 7 years ago, when standard therapy for hepatitis C was usually given for 6 months, we conducted a randomized clinical trial comparing daily vs t.i.w. treatment. In this study, 149 patients with chronic hepatitis C were randomized to received 3 MU of IFN-α either t.i.w. for 6 months or daily for 3 months followed by t.i.w. for 3 months. All patients were treated with human leucocyte IFN-α and were followed-up for up to 72 months after inclusion. Overall, patients treated daily or t.i.w. had similar rates of virological response after 3 months of induction [24/49 (50%) vs 40/100 (40%)], at the end of therapy [15/49 (31%) vs 36/100 (36%)] and at the end of follow-up [6/49 (12%) vs 9/100 (9%)]. However, when patients infected with HCV types other than HCV-1 were studied, there was a trend favouring the daily schedule that was associated with a higher [5/20 (25%) vs 5/48 (10%)] rate of long-term SR. All patients with a virological response – hepatitis C virus (HCV) RNA negative in serum as determined using the polymerase chain reaction – at 6 months after therapy remained in biochemical and virological remission at long-term follow-up, while seven of eight subjects who had normal alanine aminotransferase (ALT) levels but were serum positive for HCV RNA at 6 months, relapsed later, indicating that serum HCV RNA is better than ALT at predicting long-term cure after IFN-α therapy in chronic hepatitis C.     

Development of a hepatitis C virus relapse model using genome-length hepatitis C virus ribonucleic acid-harboring cells possessing the interferon-α-resistance phenotype

Aim:  The cure rate of current interferon (IFN) therapy is limited to approximately 50% and most of the relapses after therapy are caused by genotype-1. To develop a relapse model in cell culture, we attempted to obtain genome-length hepatitis C virus ribonucleic acid (HCV RNA) harboring cells possessing the IFN-α-resistance phenotype from previously established OR6 cells, which enabled the luciferase reporter assay for monitoring of HCV RNA replication.
Methods:  The IFN-α-resistant HCV RNA-harboring cells and control cells were obtained by the treatment of OR6 cells with and without IFN-α, respectively. Then, we examined the relapse of HCV in IFN-α-resistant HCV RNA-harboring cells.
Results:  Only type I IFN (α and β) showed significantly different anti-HCV activity between IFN-α-resistant HCV RNA-harboring cells and control cells. There was no significant difference in the anti-HCV activity of IFN-γ, fluvastatin, or cyclosporine A between the two types of cells. Furthermore, we showed that fluvastatin or cyclosporine A in combination with IFN-α could prevent the relapse after therapy in the IFN-α-resistant HCV RNA-harboring cells.
Conclusion:  We developed a HCV relapse model in cell culture using IFN-α-resistant HCV RNA-harboring cells. Thus anti-HCV reagents, which have a mechanism different from IFN-α, were shown to be useful for preventing a relapse of IFN-α-resistant HCV.     

Randomized, placebo-controlled, double-blind trial with interferon-α with and without amantadine sulphate in primary interferon-α nonresponders with chronic hepatitis C

In primary interferon-α (IFN-α) nonresponders with chronic hepatitis C, retreatment with IFN-α has only limited efficacy with sustained response rates below 10%. Therefore, the aims of the present study were to compare the efficacy and safety of IFN-α alone or in combination with amantadine sulphate in nonresponders to previous IFN-α monotherapy. Fifty-five IFN-α nonresponders with chronic hepatitis C (mean age: 46.6 years) received IFN-α 6 MIU thrice weekly for 24 weeks followed by 3 MIU thrice weekly for additional 24 weeks. Amantadine sulphate ( n =26) or a matched placebo ( n =29) was given orally twice daily for 48 weeks. Because of a low initial response rate at week 12 (13/55 patients) and a high breakthrough rate (8/13 patients) after IFN-α dose reduction in week 24, a virological end-of-treatment response with undetectable serum HCV-RNA (< 1000 copies/mL) was achieved in only five patients (IFN-α/amantadine sulphate, one patient; IFN-α/placebo, four patients). After 24 weeks follow-up a sustained virological response was observed in only two patients receiving IFN-α and placebo. Health-related quality-of-life analysis showed a substantial improvement of the Profile of Mood States (POMS) scale concerning the subscales fatigue ( P  < 0.05) and vigor ( P  < 0.05) in patients receiving combined IFN-α/amantadine sulphate treatment compared with those treated with IFN-α alone. IFN-α/amantadine sulphate combination therapy was well tolerated without any serious adverse events. In conclusion, retreatment with IFN-α and amantadine sulphate does not increase the low sustained virological response rates of IFN-α therapy in primary IFN-α nonresponders with chronic hepatitis C, but may lead to a sustained improvement of health-related quality-of-life.     

Evaluation of twice-daily administration of interferon-beta for chronic hepatitis C

To improve the efficacy of interferon (IFN) in the treatment of chronic hepatitis C, administration of IFN-beta twice per day was evaluated. Thirty-eight patients with chronic hepatitis C (26 males and 12 females, aged 25-67 years) were included. Patients were treated with a new protocol that included twice-daily treatment with IFN-beta. Three million units (MU) of IFN-beta was administered twice daily every day for 4 weeks followed by 10 MU of IFN-alpha2b, every day for 2 weeks and then three times a week for 18 weeks (total IFN-beta, 148 MU; IFN-alpha2b, 680 MU). Complete responders (CR) were defined by alanine aminotransferase levels that normalized within 6 months after completion of IFN therapy and remained normal for more than 6 months, and by serum hepatitis C virus (HCV) RNA levels that became negative as determined using the Amplicor assay. Twenty-one of 38 (55.3%) patients were CR. Nine of 21 (42.9%) patients with HCV serotype 1 were responders compared with nine of 12 (75.0%) patients with HCV serotype 2. In patients with an HCV titre greater than 1 million equivalents ml-1 (1 MEq ml-1), nine of 24 (37.5%) responded, and in patients with HCV titres less than 1 MEq ml-1, 12 of 14 (85.7%) responded. In patients with HCV serotype 1 and greater than 1 MEq ml-1 HCV RNA, four of 15 (26.7%) responded to IFN. Two-thirds (66.7%) of the patients who became negative for HCV RNA after 2 weeks of therapy responded, while 72.7% of those with positive HCV RNA after 2 weeks of therapy were non-responders. Proteinuria was frequently observed as an adverse effect of twice-daily administration of IFN-beta. The combination of twice-daily administration of IFN-beta for 4 weeks followed by IFN-alpha showed a high response rate in patients with chronic hepatitis C, but in patients with both serotype 1 and a high titre of HCV RNA, response rates were still low. Thus, the HCV RNA titre 2 weeks after starting therapy with IFN was useful for predicting the eventual response to IFN.     

Ribavirin and interferon-α combination therapy vs interferon-α alone in the retreatment of chronic hepatitis C: a randomized clinical trial

Interferon-α (IFN-α) induces sustained remission of chronic hepatitisC in approximately 25% of patients. In patients who are non-responders to the first course of therapy, retreatment with IFN-α is of limited efficacy. Ribavirin has also been used to treat chronic hepatitisC, but it induces only a transient response. In this study, we evaluated the efficacy of ribavirin and IFN-α combination therapy for IFN-α resistant chronic hepatitisC. Twenty-four IFN-α non-responders and 24 relapsers were randomized to receive either ribavirin (1000mg per day) together with IFN-α (3–6million units (MU) thrice weekly) or the same dose of IFN-α alone, for 6months. Both at the end of treatment and 6months later, normal transaminase levels were more common in the patients receiving combination therapy than in the group receiving IFN-α alone: 17 (70.8%) vs seven (29.2%) patients ( P =0.009) and six (25%) vs one (4.2%) patient ( P =0.034), respectively. At the end of treatment and 6months later, serum HCV RNA was no longer detectable in eight (33.3%) and five (20.8%) patients in the combination therapy group and in six (25%) and one (4.2%) patient in the IFN-α therapy group, respectively. Three patients (12.5%) were withdrawn prematurely from combination therapy because of side-effects; ribavirin therapy was ceased or dosage reduced in six other patients (25%), again because of side-effects. In conclusion, this combination treatment was more effective than retreatment with IFN-α, alone, in inducing sustained biochemical remission of chronic hepatitisC that was resistant to a previous course of IFN-α. The combination treatment, however, was frequently associated with significant side-effects.     

Prediction of relapse or sustained response in biochemical responders by serum hepatitis C virus RNA monitoring during interferon therapy

Normalization of serum aminotransferase levels is achieved in ≈ 50% of chronic hepatitis C patients treated with interferon (IFN); however, in about one-half of these patients the hepatitis relapses after therapy. In this study we investigated the efficacy of serum hepatitis C virus (HCV) RNA monitoring during IFN therapy to predict the outcome of a biochemical end-of-treatment (ETR) response. Eighty patients with chronic hepatitis C received leucocyte (natural) IFN-α (13 patients) or recombinant IFN-α2a (67 patients). Antiviral therapy was given for 12 months to 43 (53.7%) responders and this group was analysed further. During follow-up, 15 relapsed and 28 showed a sustained response (median follow-up 50 months, range 39–67 months). Viraemia was monitored at baseline, and at months 1, 3, 6, 9 and 12 of treatment, by nested polymerase chain reaction (PCR) (sensitivity 10–100 copies ml^–1). A combination of positive nested PCR and HCV RNA values at the 3rd and 6th months of treatment was 100% predictive of relapse (sensitivity, 66.6%; specificity, 100%). A combination of negative nested PCR and HCV RNA values at the 1st and 3rd months of treatment was 100% predictive of sustained response (sensitivity, 39.3%; specificity, 100%). In conclusion, serum HCV RNA monitoring is an appropriate and reliable tool for predicting early outcome of the biochemical ETR response after IFN discontinuation. This could be useful in the modulation of therapeutic management of chronic hepatitis C.     

Leucocyte interferon-α retreatment for chronic hepatitis C patients previously intolerant to other interferons

The activity and tolerability of a retreatment cycle with leucocyte interferon-α (IFN-α) (6 million units (MU) three times weekly for 12 months) was evaluated in a group of 22 hepatitis C patients who had been intolerant to a previous course of lymphoblastoid IFN-α. Seven patients (31%) discontinued the new therapy owing to either a lack of response (six patients) or to severe leucopenia (one patient). Fifteen patients (68%) completed the 12-month treatment: all had a biochemical response and 10 (45%) also had disappearance of serum HCV RNA (complete response). Mild adverse reactions (fever, headaches and diarrhoea) were seen in these patients during retreatment. After 12 months of follow-up, 11 patients (50%) still maintained the biochemical response (long-term response); seven of these patients (32%) were also negative for serum HCV RNA. Biochemical and complete responses, at the end of both treatment and follow-up, were similar to those seen with lymphoblastoid IFN-α. The full dose of leucocyte IFN-α, when used in patients previously intolerant to the same dosage of lymphoblastoid IFN-α, was better tolerated: only one of the 15 patients who completed the 12-month treatment had a severe adverse event leading to withdrawal vs 22 of 68 patients treated with lymphoblastoid IFN-α. Furthermore, there were no manifestations of serological or clinical autoimmunity caused by leucocyte IFN-α, even in patients with autoantibodies associated with previous IFN therapy.     

Predictive value of IgM antibodies to hepatitis C virus in patients with chronic hepatitis C undergoing interferon-α therapy. Analysis by two different methods

SUMMARY. To determine the predictive value of IgM anti-hepatitis C virus (HCV) testing in patients with chronic hepatitis C infections undergoing interferon-α (IFN-α) therapy, IgM anti-HCV reactivity was analysed by two different methods (non-commercial and commercial) in 19 patients and monitored at times 0 (pre-treatment), 3, 6, 12. and 24 months during follow-up. Eight patients were non-responders, five remained in sustained response 1 year after stopping treatment, and six had a relapse. No correlation between alanine transaminase (ALT) levels and IgM anti-HCV reactivity was found by either method in baseline samples. In addition, neither the presence nor absence of IgM anti-HCV in baseline samples, nor the loss of specific IgM reactivity during treatment, had any predictive value. Finally, no other parameters analysed (age, sex, risk group and histological diagnosis), were significantly associated with IgM anti-HCV reactivity in our study. In summary, these results suggest that baseline detection and monitoring of IgM anti-HCV reactivity are not useful in predicting the sustained response to IFN-α therapy in chronic hepatitis C infection.