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.     

Long-term titrated recombinant interferon-α2a in chronic hepatitis C: a randomized controlled trial

Summary. The efficacy and tolerability of 12-month treatment with titrated doses of recombinant interferon-α2a (IFN-α2a) in chronic hepatitis C were studied in 67 consecutively recruited patients randomly assigned either to a starting dose of IFN-α2a 6 MU, subsequently adjusted to the serum alanine aminotransferase (ALT) response ( n = 35), or to no therapy ( n = 32; controls). End-of-treatment ALT levels were normal and hepatitis C virus (HCV) RNA was negative by nested polymerase chain reaction (PCR) in 17 (49%) treated patients compared to none of the controls ( P < 0.001). During the 12 months after stopping treatment the number of patients who remained in remission was eight (23%) and one respectively (4%) ( P = 0.031). Follow-up liver biopsy showed reduced hepatic inflammation in 80% of treated patients and in 29% of controls ( P < 0.001). The eight sustained responders and 2 7 non-responders or relapsers received similar mean total doses of IFN (565 MU vs 545 MU) and had a similar incidence of anti-IFN neutralizing anti-bodys (13% vs 19%). Absence of cirrhosis was the only independent pretreatment parameter that predicted a sustained response. In conclusion, a mean cumulative dose of IFN 549 MU, titrated over 12 months, was well tolerated, and resulted in the long-term clearance of HCV RNA and normal ALT levels in 23% of patients.     

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.     

Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance

The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-γ prior to initiation of interferon-α treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-α treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-γ (1 MIU/day) was administered daily for 14 days followed by natural IFN-α (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-α treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-γ administration, and tended to return to the pretreatment level after the start of IFN-α administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN-γ prior to the initiation of IFN-α treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.     

Long-term administration of interferon-α in non-responder patients with chronic hepatitis C: follow-up of liver fibrosis over 5 years

In chronic hepatitis C, previous data have shown that short-term treatment with interferon-α (IFN-α) can reduce collagen deposition in the liver independently of the viral response. The aim of this work was to determine, in non-responder patients, the long-term effect of IFN-α on liver fibrosis according to the total administered dose and the fibrotic stage. Fibrosis was investigated on liver biopsies from 24 non-responder patients with chronic hepatitis C retreated with successive courses of IFN-α. The degree of liver fibrosis was assessed on three successive biopsies, performed before IFN-α treatment and 1 and 5 years later, in 13 and 11 patients, respectively, treated for less (mean: 7.5 months, 313 MU) and more (mean: 21.8 months, 791 MU) than 1 year. For each biopsy, fibrosis was assessed using a histological semiquantitative fibrosis scoring system and by morphometry after picrosirius red staining. Regardless of the dose and duration of IFN-α therapy, a slight decrease of fibrosis was observed in patients 5 years after starting treatment. In cirrhotic patients, a short treatment induced an improvement followed by a relapse of fibrosis in 57%, and only 43% of patients showed constant collagen regression over the 5 years of follow-up. On the contrary, after prolonged therapy, a progressive and significant decrease occurred throughout the follow-up period in all patients ( P = 0.045). Long-term treatment with IFN-α is therefore associated with regression of liver fibrosis, particularly in cirrhotic patients. These promising results need to be confirmed in a larger series of patients.     

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.     

Response to interferon-α of Egyptian patients infected with hepatitis C virus genotype 4

Summary. Hepatitis C virus (HCV) genotype 4 is the principal HCV genotype found in Egypt and the Middle East. Little is known concerning its propensity to cause disease and the frequency with which infected individuals respond to interferon-α (IFN-α). We have investigated the response to treatment in a cohort of 100 chronic hepatitis C patients infected with genotype 4. All patients had biopsy-proven chronic active liver disease. Each was treated with 3 million units (MU) IFN-α, thrice weekly. Response was monitored, in 92 patients who completed treatment, by alanine aminotransferase (ALT) measurements and by polymerase chain reaction (PCR) for HCV. ALT levels remained abnormal in 64 patients during treatment (69.6%). Of the 28 patients who showed a biochemical response during treatment (30.4%), 18 maintained this over the 6-month post-treatment period. Amongst the sustained biochemical responders, HCV RNA was cleared from serum in only four of the 18 (22.2%) in this period. Histological improvement was observed in 26/51 (50.9%) of the patients who had a second biopsy.
Hence, patients infected with HCV genotype 4 show a poor response to IFN-α therapy compared with genotypes 2 and 3, but a similar response to IFN-α compared with those infected with type 1b HCV. These findings have major implications for treatment strategies in the Middle East, including Egypt, where HCV genotype 4 is widely distributed.     

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.     

Histological and virological long-term outcome in patients treated with interferon-alpha2b and ribavirin for chronic hepatitis C

Long-term virological and histological outcome following interferon-α2b (IFN-α2b) and ribavirin treatment for 24 weeks was studied in 20 patients with chronic hepatitis C who were without a lasting response to IFN as monotherapy. Following combination therapy, sustained virological response (SR) was achieved in 12 patients (i.e. hepatitis C virus (HCV) RNA negative in serum 6months post-treatment). Eleven of these patients remained HCV RNA negative in serum 2 years post-treatment. A virological long-term response (LTR) was more frequent in patients with a previous end-of-treatment response to IFN monotherapy than in non-responders. Liver histology at follow-up, ≥24months post-treatment, showed substantial improvement in patients with a virological LTR to the combination treatment. In all nine patients biopsied at the 2-year follow-up, liver inflammation had disappeared totally (grade=0), and the stage (fibrosis) had improved. In contrast, no significant changes in grade or stage were noted in patients with a virological non-LTR to combination treatment. A significant improvement in inflammation was noted, in patients with a virological LTR, from 3.6 to 0.2 ( P <0.01) and in fibrosis from 2.0 to 1.4 ( P <0.05) whereas the corresponding scores for patients with a virological non-LTR did not change significantly, from 3.1 to 1.5 for inflammation and for fibrosis from 1.3 to 1.3. We conclude that patients with chronic hepatitis C who achieve a virological sustained response 6months post-treatment with IFN-α2b and ribavirin will remain virological responders for a follow-up period of least 24months, concomitant with a disappearance of inflammatory activity and a marked improvement of fibrosis in the liver.     

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.     

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.     

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.     

Development of Thyroid Autoimmunity after Administration of Recombinant Human Interferon-α2b for Chronic Viral Hepatitis

To investigate the frequency and clinical characteristics of autoantibody formation and development of autoimmune thyroid disease after interferon therapy, we measured the autoantibodies to thyrotropin receptor (TBII), thyroglobulin (ATA), and microsomal antigen (AMA) in 28 patients with histologically proven chronic viral hepatitis [25 males, three females; mean age 38.7 ± 8.7 (SD) yr] receiving recombinant interferon-α2b (IFN-α) treatment. Twenty patients with chronic hepatitis B (positive for HBsAg, HBeAg, and HBV DNA) and eight patients with chronic hepatitis C (positive for anti-HCV and HCV RNA) received IFN-α, 3 million units subcutaneously, three times a week for 6 months. Before, during, and up to 6 months after IFN-α therapy, thyroid hormone levels and titers of AMA, ATA, and TBII were measured every 2 months. None of them had thyroid dysfunction or antithyroid autoantibodies before IFN-α treatment. A 34-yr-old male patient developed Graves'disease during the last month of therapy. He required long-term antithyroid medications, even after discontinuation of IFN-α. Another 44-yr-old female patient developed AMA during IFN-a treatment; however, thyroid function remained normal and goiter did not develop in this patient. No other patient developed thyroid autoantibodies and thyroid dysfunction. In summary, only a small minority of patients will develop thyroid autoimmunity during IFN-α therapy, and much less often with this low dose of IFN-α.     

Pilot study of interferon-alpha and ribavirin treatment in patients with chronic hepatitis C and normal transaminase values

Combination interferon-α (IFN-α) and ribavirin treatment has become standard therapy for patients with chronic hepatitis C and elevated transaminase levels (> 1.5 × upper limit of normal). No previous study has specifically examined the efficacy of this treatment in patients with normal transaminase values. In this pilot study, we treated 19 patients, with normal or near-normal ALT values on at least three occasions, and histologically mild disease, with induction IFN-α2b, 5 mega units daily for 4 weeks, then 3 mega units thrice weekly for 44 week, plus concomitant ribavirin 1000 mg or 1200 mg daily for 48 weeks. Nine of the 19 (47%) showed sustained virological response, defined as undetectable HCV-RNA at 24 weeks after the end of treatment. No ALT flares were observed in any patient. We conclude that combination induction IFN-α and ribavirin therapy may be effective in patients with normal-ALT, and appears not to induce flares of ALT activity. Controlled trials of this treatment in this subgroup of patients with hepatitis C are warranted.     

Coinfection with hepatitis B and C or B, C and δ viruses results in severe chronic liver disease and responds poorly to terferon-a treatment

SUMMARY. Chronic coinfection with the hepatitis B (HBV) and hepatitis δ (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-α2b (IFN-α) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied: 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-α2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and δ coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone. Short-and long-term responses to doses of IFN-α that are used to treat HCV are infrequent, but further studies are required to determine whether higher-dose IFN-α may benefit patients with combined hepatitis virus infections.     

Early Loss of Serum Hepatitis C Virus RNA Can Predict a Sustained Response to Interferon Therapy in Patients with Chronic Hepatitis C

Objectives : We evaluated whether the loss of serum hepatitis C virus (HCV) RNA early in interferon (IFN) therapy would indicate a subsequent response to IFN therapy. Methods : One hundred fourteen patients with chronic hepatitis C were treated with IFN-α for 24 weeks. All patients were positive for anti-HCV antibodies and serum HCV RNA. Serum HCV RNA was measured by highly sensitive and specific RT-PCR (modified Amplicor HCV). Results : Of 114 patients who were treated with IFN-α for 24 weeks, 22 of 29 patients (75.9%) who lost HCV RNA at the first week of treatment, 5 of 14 patients (35.7%) who lost HCV RNA at the second week, and 2 of 16 patients (12.5%) who lost HCV RNA at fourth week were judged as sustained responder (SR). The SR rate was significantly higher in patients who lost HCV RNA at the first week of therapy ( p < 0.05). On the contrary, none of 55 patients who retained HCV RNA during the first 4 weeks of IFN therapy were judged as SR. Concerning the patients who lost HCV RNA at the first week of therapy, there were no significant differences in the SR rate in either HCV genotype (1b, 2a, and 2b). Conclusions : Our study confirms that the early response to IFN (loss of HCV RNA at the end of the first week of IFN therapy) can be a predictor of the subsequent sustained response to IFN therapy. Additionally, positivity of HCV RNA at the fourth week of IFN therapy can be a predictor of the subsequent non-sustained response to IFN therapy.     

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.     

Consensus interferon: a novel interferon for the treatment of hepatitis C

Although alpha interferons are currently the only therapies approved for treatment of HCV infection approximately half of the treated patients do not respond to the standard regimen of IFN-α-2b 3 MU administered 3 times per week (tiw) for 6 to 12 months. Of those who do demonstrate a response, 50–80% will relapse within 6 months after treatment cessation. Thus, the overall response to treatment is low. This paper focuses on studies that have been conducted with a newly developed interferon, Consensus Interferon (CIFN), in the treatment of chronic Hepatitis C. This type-1 interferon links the most common occurring amino acid sequences at each position of available natural alpha interferons into one 'consensus' protein. The thus synthesized molecule shows a 10-fold higher in vitro biological activity as compared to single recombinant IFN-α-2b or IFN-α-2a, possibly due to its greater binding affinity to interferon receptors. In patients with chronic hepatitis C, CIFN 9 μg, three times weekly for 24 weeks, proved to be equally efficacious and as safe as IFN-α-2b, but compared to 3 MU IFN-α-2b, CIFN 9 μg demonstrated improved responses in patients with high baseline viral titres.     

Sustained response to interferon-alpha2a monotherapy of young blood donors with minimal-to-mild chronic hepatitis C. The Donor Surveillance Study Group

Subjects with minimal-to-mild chronic hepatitis C may suffer long-term consequences of hepatitis C virus (HCV) infection. Nonetheless, they are not candidates for antiviral treatment, mainly because little data are available concerning the efficacy and safety of therapy. Thirty-two HCV RNA positive individuals aged 18–45 years, who had a histological activity index score ≤ 8 and alanine aminotransferase (ALT) levels ≤ 1.5 times lower than the normal limit for at least 1 year, were prospectively enrolled among a cohort of 35358 candidate blood donors, and treated with 4.5 mega units (MU) of recombinant interferon-α2a (IFN-α2a) thrice weekly for 6 months, and for an additional 6 months if a virological response was observed. Twelve months after the completion of treatment, 13 of 31 evaluable patients were HCV RNA negative, accounting for a sustained response rate of 42%. Patients without fibrosis had a lower response rate than those with mild fibrosis (two of 14 vs 11 of 17; P =0.012). In responders, median aminotransferase levels were significantly lower after therapy than before (11.04 ± 3.98 vs 27.3 ± 12.32 U l⁻¹, respectively; P  < 0.005). When the analysis was limited to the six responders whose pretreatment aminotransferase levels were consistently normal, this difference was still significant (9.33 ± 4.12 vs 20.58 ± 6.73 U l⁻¹; P =0.002). In conclusion, a durable suppression of viraemia can be obtained by IFN monotherapy in a relatively high proportion of young subjects with minimal-to-mild chronic hepatitis C, especially when portal fibrosis is found on liver biopsy. The disappearance of viraemia always leads to a reduction in the degree of hepatocellular necrosis.