Interferon-alpha Therapy For Chronic Hepatitis Research Articles

Involvement of dendritic cells frequency and function in outcomes of interferon-alpha therapy for chronic hepatitis B patients

To elucidate the change in frequencies and functions of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) before and after interferon-alpha therapy for chronic hepatitis B (CHB) patients, and its correlation with virological and biochemical data. Thirty patients with HBeAg-positive CHB who underwent IFN-alpha therapy were examined. Frequencies and expression of CD86 of mDC and pDC of peripheral blood were measured at baseline and treatment week (TW) 12 by flow cytometry. According to biochemical and virological parameters, the 30 patients were divided into ALT normalized group, ALT non-normalized group and virological responder group, virological non-responder group respectively. Statistical analysis of DC changes among different groups at baseline and TW12 was proceeded. (1) In the ALT normalized group, the pDC frequency at TW12 (0.25 +/- 0.14%) was higher than that at baseline (0.18 +/- 0.09%) (P = 0.023); in the ALT non-normalized group, the mDC frequency (0.58 +/- 0.34%) and its surface CD86 expression (61.80 +/- 22.52%) decreased significantly as compared with baseline (0.88 +/- 0.51%, 79.92 +/- 25.94%, respectively), (P = 0.025, P = 0.036, respectively). (2) In the virological responder group, the CD86 expression on pDC at TW12 (46.86 +/- 12.22%) was higher than that at baseline (29.42 +/- 15.16%) (P = 0.002); in the virological non-responder group, the mDC frequency (0.51 +/- 0.22%) and its surface CD86 expression (59.63 +/- 22.94% ) decreased significantly as compared with baseline (0.94 +/- 0.58%, 80.11 +/- 29.34%, respectively), (P = 0.006; P = 0.049, respectively). In IFN-alpha therapy for CHB patients, the increments of pDC frequency and function were related to biochemical and viral response, and decreases of mDC frequency and function were related to non-biochemical and non-viral response.

Alpha-interferon therapy for chronic hepatitis C may induce acute allograft rejection in kidney transplant patients with failed allografts

In hepatitis C virus (HCV) positive kidney transplant (KT) patients, the use of alpha-interferon (alphaIFN) is contraindicated due to the risk of acute rejection (AR). Conversely, if these HCV(+) KT patients lose their allograft, re-transplantation might be contemplated provided alphaIFN therapy has been attempted. Between 01/01/1989 and 31/12/1994, 261 kidney transplantations were performed; of these 174 were HCV(-) (group I) and 87 were HCV(+) (group II). At last follow-up (2006), in group I, the number of patients with a functioning graft, the number of patients who died with a functioning graft, and the number of patients who lost their graft before or after month (M) 12 were 92 (52.8%), 14 (8%), 20 (11.5%) and 48 (27.7%), respectively. In group II, the corresponding figures were 22 (25.3%; P < 0.0001), 8 (9.1%; ns), 9 (10.3%; ns) and 48 (55.3%; P < 0.0001). In group I, 19 of 48 (39.5%) patients with failed allografts after M12 underwent transplantectomy (TX) compared to 14 of 48 (29%; ns) in group II. In group II, 11 of 48 (23%) patients were offered alphaIFN therapy after their allograft failed: of these, four (36.3%) developed AR during alphaIFN therapy leading to TX. Histology, in addition to chronic allograft lesions, showed acute cellular and vascular lesions. In patients who were not offered alphaIFN therapy, TX was performed less frequently, i.e. in only six cases (16.2%). We conclude that even alphaIFN-treated KT patients with a failed allograft can experience acute allograft rejection that requires transplantectomy during therapy.

Poor response to 18‐month lamivudine monotherapy in chronic hepatitis B patients with IgM anti‐HBc and acute exacerbation

Appearance of immunoglobulin class M antibody against hepatitis B core antigen is a predictor of beneficial response to interferon-alpha therapy in chronic hepatitis B patients, but its relationship with the efficacy of lamivudine therapy remains unclear. To investigate the outcome of lamivudine therapy in chronic hepatitis B patients with immunoglobulin class M antibody against hepatitis B core antigen and acute exacerbation. Chronic hepatitis B patients with acute exacerbation receiving a national-wide therapeutic trial of 18-month lamivudine monotherapy were enrolled for the analysis. Four consecutive seronegative patients were recruited as individual matching controls of one positive subject. Immunoglobulin class M antibody against hepatitis B core antigen in serum was assayed monthly by an automated microparticle enzyme immunoassay. Fifteen (8.9%) of 167 chronic hepatitis B patients with acute exacerbation were seropositive for IgM anti-HBc. Thus 60 seronegative patients were consecutively recruited as control group. At the end of therapy, two (13.3%) of the 15 seropositive patients achieved a sustained response, significantly lower than 26 (43.3%) of the control group. Appearance of immunoglobulin class M antibody against hepatitis B core antigen in chronic hepatitis B patients with acute exacerbation is a predictor of poor response to lamivudine monotherapy. This is clinically relevant to the decision-making in treating chronic hepatitis B patients with acute exacerbation.

Influence of HLA-DRB1 alleles and HBV genotypes on interferon-α therapy for chronic hepatitis B

To investigate the influence of HLA-DRB(1) alleles and HBV genotypes on interferon-alpha therapy for chronic hepatitis B. HLA-DRB1*03, *07, *09, *12, *15 alleles were determined using polymerase chain reaction/sequence specific primer (PCR/SSP) technique in 126 patients with chronic hepatitis B and 76 normal control subjects in Shandong Province, and HBV genotypes were determined by nested-PCR analysis using type-specific primers in 126 patients. The positivity of HLA-DRB1*07 allele in chronic hepatitis B group was significantly higher than that in normal control group (chi(2) = 6.33, P<0.025, RR = 2.37). Among the 126 patients, genotype B was found in 38 (30.2%), genotype C in 69 (54.8%), and mixed genotype (B+C) in 19 (15.0%), genotypes D-F were not found. Among the 46 DRB1*07(+) patients, 7 were responders and 39 were non-responders among them (chi(2) = 6.71, P<0.05). The positivity of HLA-DRB1*07 and prevalence of HBV genotype C were significantly higher in non-responders than in responders. High positivities of HLA-DRB1 *07 allele and HBV genotype C are closely associated with the lower response to interferon-alpha therapy for chronic hepatitis B.

A prospective study on treatment of chronic hepatitis C with tailored and extended interferon-alpha regimens according to pretreatment virological factors

Hepatitis C virus genotype and viral loads are important predictors for sustained virologic response (SVR) to interferon-alpha therapy for chronic hepatitis C (CHC). We have conducted a prospective study on treatment of 90 patients with a tailored-dose and extended interferon-alpha regimen according to pretreatment virologic factors (low-risk, genotype non-1b/viral loads≤0.65 Meq./ml, 6 million units thrice weekly for 12 weeks (6 MU×12 weeks) followed by 3 MU×24 weeks; high-risk, genotype 1b/viral loads>0.65 Meq./ml, 6 MU×24 weeks followed by 3MU×24 weeks; medium-risk, the others, 6MU×12 weeks followed by 3 MU×36 weeks), and compared to 123 patients with fixed-dose regimen (6 MU×24 weeks). Patients with tailored-dose regimen had a significantly higher rate of SVR than those receiving fixed-dose interferon-alpha (46.7% versus 29.3%, P<0.01, intention-to-treat analysis). Improved efficacy was mainly seen in the medium-risk (48.9% versus 26.6%, P=0.02) and the high-risk groups (26.1% versus 8.3%, P=0.06), but not in the low-risk group. By using multivariate logistic regression, low pretreatment viral loads and tailored-dose IFN regimens were significantly associated with higher SVR in both the high- and medium-risk groups. There were no differences in the tolerability and in the incidence of adverse effects between fixed-dose and tailored-dose groups. In conclusion, our results demonstrate the efficacy of tailored-dose interferon-alpha therapy for CHC; these could provide decision-making information for standard/pegylated interferon-alpha combining ribavirin therapy according to baseline predictors.

Sarcoidosis associated with interferon-alpha therapy for chronic hepatitis B

Sarcoidosis is one of the possible rare complications of interferon-alpha (IFN-alpha) therapy. Only a few reports have been published on this disease, and these have been associated with the treatment of malignant diseases, essential thrombocytosis, and chronic hepatitis C. We report on a 64-year-old man with chronic hepatitis B (HBsAg, HBeAg, HBV DNA-positive) who was treated with recombinant IFN-alpha-2b (5 MU three times weekly) for 28 weeks. Tolerance to treatment was very good; only a mild flu-like syndrome appeared. Twelve months after completing the therapy, a chest X-ray was performed that revealed bilateral hilar masses, and high-resolution computed tomography (HRCT) of the chest indicated the presence of lymphadenopathy of the anterior and middle mediastinum. Therefore, a right-sided thoracoscopy was performed with excision of a 27-mm lymph node and a histological diagnosis of sarcoidosis was made. No medication for sarcoidosis was indicated. Complete normalization of mediastinal lymphadenopathy (verified on HRCT and chest X-ray) was confirmed 1 year following the thoracoscopy. To our knowledge, this is the first case wherein occurrence of sarcoidosis in a chronic hepatitis B patient treated with IFN-alpha is described. We suppose that IFN-alpha, as a potent stimulator of T-helper 1 (Th1) immune responses, may trigger the compartmentalized Th1 reaction that has been shown to take place in sarcoidosis.

Interferon-associated retinopathy in a uniform regimen of natural interferon-alpha therapy for chronic hepatitis C.

The development of retinal lesions induced by a uniform regimen of interferon-alpha therapy for chronic hepatitis C was prospectively investigated. Eighty-one patients received 6 mega units of natural interferon-alpha intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of interferon-alpha administered was uniformly 478 mega units per patient. Two expert ophthalmologists prospectively examined the patients for retinal lesions before, during and after the therapy. Retinopathy was not found in comparison groups or any of the patients before treatment. In total 34.6% (28/81) of the patients showed cotton-wool spots or minor retinal hemorrhage, or both lesions, during therapy, but these lesions were reversed during or after interferon therapy. The occurrence rates of cotton-wool spots alone, retinal hemorrhage alone and both lesions were 13.6% (11/81), 6.2% (5/81), and 14.8% (12/81), respectively. The appearance of retinopathy did not correlate with patients' background including viral loads and response to the therapy, but was more frequently found in older patients and patients with hypertension and/or diabetes mellitus; disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared 2-4 months after the start of the therapy, and the severity of the lesions did not differ between patients with and without hypertension and/or diabetes mellitus. Although it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alpha.

Interferon-alpha therapy for chronic hepatitis B: Early response related to pre-treatment changes in viral replication

Chronic hepatitis B patients with low pre-treatment HBeAg (and HBV-DNA) levels are more likely to respond to interferon-alpha therapy. In retrospect, this low level of HBeAg may have been reached just before the start of therapy. Pre-treatment changes in HBeAg levels were studied in 121 patients undergoing interferon-alpha 2B therapy. HBeAg was monitored by the AxSYM HBe 2.0 Quantitative (Abbott Laboratories) and HBV-DNA by liquid hybridisation (Abbott Laboratories). At the end of treatment (week 16) 24 patients had responded (HBeAg and HBV-DNA below the level of detection). Response was significantly (P = 0.007) related to a decrease in HBeAg level before the start of therapy. Eight of the 24 (33%) responding patients exhibited a > 50% decrease in HBeAg level just before the start of therapy compared to 7 of the 97 (7%) non-responding patients. The geometric mean titre of HBeAg decreased significantly (P < 0.005; 8-week period before start) among responding patients (271 ( 98 PEI U/ml) in contrast to non-responding patients (737 ( 724 PEI U/ml). Planning the start of interferon treatment just after a spontaneous decrease in HBV replication may increase the response rate for interferon-alpha therapy.

Interferon/antioxidant combination therapy for chronic hepatitis C—a controlled pilot trial

The effects of two forms of antioxidative co-therapy were analyzed in 24 interferon-alpha (IFN)-naive patients with chronic hepatitis C who were randomized to either receive IFN monotherapy (3×4.5 million units IFN-α 2a per week), (group A), or IFN and N-acetylcysteine ( N-acetylcysteine (NAC) 1.800 mg/day) plus sodium selenite (400 μg/day) supplementation (group B), or treatment as in group B plus vitamin E (544 IU/day) (group C), over 24 weeks. Changes in histology, normalization of ALT, reduction of viral RNA, serum levels of glutathione, selenium, vitamin E, erythrocyte glutathione peroxidase, trolox equivalent antioxidative capacity (TEAC), thiobarbituric acid reactive substances (TBARS) and protein carbonyl groups were measured. Low baseline TEAC and elevated TBARS indicated increased oxidative stress before therapy, which was not affected by antioxidant supplementation. At the end of treatment complete responses were found in 3/8, 2/8 and 6/8 patients in groups A, B and C, respectively, but liver histology had not significantly improved. Vitamin E treated patients had a 2.4 greater chance (95% CI: 1.05–5.5) of obtaining a complete response and had significantly greater reduction in viral load ( P=0.028) than patients without vitamin E. Relapses, i.e. re-appearance of detectable hepatitis C virus (HCV) RNA and/or re-elevation of ALT-activity occurred in 7 out of the 11 responders within 6 months after termination of therapy (group A: 2/3, group B: 1/2 and group C: 4/6). Thus, no overall beneficial effect of antioxidant/IFN therapy was detected. However, the apparent trend towards a more favorable outcome with vitamin E supplementation warrants to further study this substance as an adjuvant to IFN therapy in chronic hepatitis C.

Viral and host factors in the prediction of response to interferon-alpha therapy in chronic hepatitis C after long-term follow-up.

Acute infection with hepatitis C virus (HCV) develops into a chronic hepatitis in about 50-70% of patients. Treatment of these patients with interferon-alpha (IFN-alpha) results in a sustained long-term response in only 15-20% but causes numerous unwanted side-effects in a higher percentage of patients. The aim of our study was to define host or viral parameters that would allow identification of responders and non-responders to IFN-alpha prior to the onset of treatment. We studied a group of 87 patients suffering from chronic hepatitis C who were treated with IFN-alpha. After long-term follow-up, 18 patients (21%) showed a sustained response to IFN-alpha therapy (normalization of serum transaminases and loss of viral RNA from serum) for up to 7 years after therapy had ceased. By univariate and multivariate analyses, no host factors were found to be predictive of response to therapy. Neither the degree of inflammation or fibrosis in liver biopsy samples obtained before treatment nor immunogenetic factors (major histocompatibility complex II haplotype and tumour necrosis factor-alpha promoter polymorphism) were associated with response to therapy. In contrast, viral parameters showed a strong association with response to therapy. HCV genotype 3 was found significantly more frequently in responders (P = 0.034), and mean HCV RNA concentration was lower in responders (3.1 x 10(4)) than in non-responders (2.5 x 10(5)) (P = 0.01). By multivariate analysis, both HCV genotype and HCV RNA concentration were independent predictors of response to therapy. However, exact prediction of response to treatment for an individual patient was not possible on the basis of pretreatment viral RNA concentration or viral genotype. The best association with response to therapy was found to be clearance of HCV RNA from serum 3 months after the start of treatment (32 of 34 partial and sustained responders vs 0 of 53 non-responders; P = 0.001). In conclusion, determination of pretreatment viral factors, but not host factors, was significantly correlated with treatment response but did not give an accurate prediction for patients, whereas clearance of HCV RNA from serum after 3 months of therapy was predictive of response to therapy.

Viral kinetics can predict early response to alpha-interferon in chronic hepatitis C.

Response rates to alpha-interferon therapy for chronic hepatitis C are poor. An early indication of efficacy would reduce the need for prolonged therapy, leading to significant cost savings. It was established that a change in quantitative hepatitis C virus RNA (HCV-RNA) titre at 4 weeks could predict the outcome of alpha-interferon therapy in chronic hepatitis C. Serum HCV-RNA titres were quantified using branched chain DNA (bDNA) assay in 26 patients who responded to alpha-interferon (serum HCV-RNA negative after 12 weeks therapy) and 11 age and sex matched non-responders. Quantitative bDNA and qualitative RT-PCR assays for HCV-RNA were measured pretreatment and at 4 weeks. The change in quantitative HCV-RNA titre between pre-therapy and after 4 weeks was compared in the two groups. Seventeen of the 37 patients had become RT-PCR negative at 4 weeks (early responders) and had an undetectable HCV-RNA titre on bDNA assay. Nine patients were RT-PCR positive at 4 weeks but negative by 12 weeks (delayed responders), and of these, 8 had an undetectable viral titre at 4 weeks on bDNA assay. The patient with a detectable HCV titre did become RT-PCR negative after 12 weeks, but subsequently became RT-PCR positive again at 24 weeks. All the non-responders had a detectable bDNA titre (> 0.2 Meq/ml) at 4 weeks. Change in quantitative HCV-RNA titre measured by bDNA assay at 4 weeks predicts response to alpha interferon. If HCV-RNA remains detectable on bDNA assay at 4 weeks, no sustained response to treatment is found and alpha-interferon can be discontinued.

Effectiveness of interferon-alpha therapy in chronic hepatitis C is associated with the amount of interferon-alpha receptor mRNA in the liver

Background/Aims: This study aimed to investigate the relationship between interferon-α receptor mRNA in the liver and the response to interferon therapy in chronic hepatitis C. Methods: Interferon-α receptor mRNA was quantified by reverse transcription polymerase chain reaction using liver biopsies from 40 patients, comprising 20 responders and 20 non-responders to subsequent interferon therapy. Results: The amount of interferon-α receptor mRNA was significantly larger in interferon-responders (0.72±0.12) than non-responders (0.26±0.08) ( p<0.01). Regardless of the response to interferon, histological activity index scores and the amount of HCV-RNA showed significant inverse correlation to the amount of interferon-α receptor mRNA, whereas the HCV-RNA genotype was not associated with the amount of interferon-α receptor mRNA. Logistic analysis and multiple regression analysis showed that the amount of interferon-α receptor mRNA was significantly associated with the efficacy of interferon ( p=0.0275), but not with fibrosis of the liver ( p=0.2726). Conclusions: Our results suggest that the amount of interferon-α receptor mRNA is an important factor determining the response to interferon, and may be a new predictor of interferon response in chronic hepatitis C.

Permanent response to alpha-interferon therapy in chronic hepatitis C is preceded by rapid clearance of HCV-RNA from serum

Background/Aims: Prediction of response to interferon therapy is important in the management of chronic hepatitis C. Pre-therapy data are valuable but they may be inaccurate in some cases. Our aim was to investigate whether the biochemical and virological events that occur early during interferon therapy in chronic hepatitis C may predict the final result of the treatment. Methods: ALT and serum HCV-RNA were serially measured in 53 HCV-RNA-positive patients who received a standard 6-month course of interferon therapy. Eleven patients with a sustained response, 23 who responded but subsequently relapsed and 19 who did not respond were studied. HCV-RNA was measured with a commercial kit (Amplicor HCV). Results: After 4 weeks of treatment, HCV-RNA became negative in 73% of sustained responders, in 26% of transient responders ( p=0.02) and in none of the non-responders. Corresponding figures after 8 weeks of therapy were 82% in sustained responders, 61% in transient responders and 9% in non-responders. The difference between sustained and transient responders at this times was not significant. After 4 weeks of therapy, 82% of sustained responders, 52% of transient responders and none of the non-responders presented normalization of alanine transferase. The difference between sustained and transient responders was not significant. Corresponding figures for normalization of alanine transferase at 8 weeks were 82%, 96% and 0% respectively. At the end of treatment, all sustained responders, 70% of transient responders and none of the non-responders had cleared HCV-RNA from serum. Conclusions: A rapid normalization of alanine transferase induced by interferon therapy is associated with response, but does not differentiate between transient and permanent response. In contrast, clearance of HCV-RNA after 4 weeks of treatment, but not after 8 weeks, is significatively associated with sustained response. Testing for HCV-RNA early during interferon administration may be valuable for further decisions concerning therapy in patients with chronic hepatitis C.

Interferon-α therapy for chronic hepatitis C in special patient populations

Interferon-alpha therapy for chronic hepatitis C in special patient populations raises a number of issues. Patients with hemophilia, kidney disease requiring hemodialysis, mixed cryoglobulinemia, HIV infection, and those receiving an allograft share some characteristics that complicate the treatment of hepatitis C virus infections. These patients generally have some degree of immune deficiency, higher levels of hepatitis C virus replication, and are infected with genotypes 1a or 1b. Each of these characteristics is often associated with a poor response to interferon therapy. Clinical research in this area also has been limited. Current data and clinical experience demonstrate that interferon-alpha therapy should be considered in patients with hemophilia who have concurrent hepatitis C viral infection. Other hepatitis C virus-infected patient populations in which interferon-alpha therapy may be beneficial include those undergoing hemodialysis, mixed cryoglobulinemia, or HIV infection. Further, the high incidence of relapse following treatment cessation in these patients warrants prolonged administration of interferon-alpha. Patients undergoing renal or hepatic allograft transplantation who develop hepatitis C virus infections are not as likely to benefit from interferon-alpha therapy. These patients may be at risk for allograft rejection during interferon treatment.

Serological markers of autoimmunity in renal transplant patients before and after alpha-interferon therapy for chronic hepatitis C.

Chronic hepatitis C is the major cause of chronic liver disease after successful cadaveric renal transplantation. The aims of this prospective, open study were to assess in such a population, firstly the prevalence of different organ-specific and nonspecific antibodies and related disorders, and secondly their outcome after inteferon-alpha therapy as well as the incidence of new immunologic disorders under and after this therapy. In 15 cadaveric renal transplant patients (10 men, 5 women, ages 29-65 years) with chronic hepatitis C and histological features of chronic active hepatitis, undergoing chronic immunosuppression (ciclosporine A with or without steroid and azathioprine) and treated with recombinant alpha 2b-interferon (IFN alpha) (mean duration 142 +/- 35 days), we assessed before and after this therapy the serum levels of cryoglobulinemia, rheumatoid factors (RF), thyroid-stimulating hormone (TSH), free thyroxine (fT4), and antinuclear (ANA), antismooth muscle (ASMA), antimitochondrial (AMA), anti-LKM1, antimicrosomal thyroid (MCA), antithyroglobulin (TGA) autoantibodies. At the start of IFN alpha therapy, 14 of 15 patients had detectable autoantibodies (RF: 9; ANA > 1/50: 8; ASMA > 1/50: 4; other autoantibodies: 0); 1 had cryoglobulinemia. At the end of therapy the cryoglobulinemia had disappeared, the preexisting autoantibodies remained present in all patients but 2; 3 patients had developed MCA without evidence of clinical or biological thyroid abnormalities and 3 others had developed either RF (1) or ANA (1) or ASMA (1), without any related symptoms. One patient developed transient type II diabetes mellitus without anti-Langerhans beta-cell antibodies. Finally, the occurrence of autoantibodies in our patients was associated either with HLA DR3 or DR4 or DR7 phenotypes. We found that the prevalence of extrahepatic immunologic abnormalities was high in renal transplant patients with chronic hepatitis C and no exacerbation was observed during of after IFN alpha therapy. The most frequent autoantibody appearing after IFN alpha therapy was MCA although without thyroid abnormalities.

Acute renal failure associated with alpha-interferon therapy for chronic hepatitis B

Acute renal failure associated with alpha-interferon therapy for chronic hepatitis B

Autoimmunity during alpha-interferon therapy for chronic hepatitis C

One hundred twenty-five patients with chronic hepatitis C were treated with natural IFN alpha or recombinant IFN alpha-2a, daily doses of 3 MU or 9 MU, respectively. IFNs were given 6 times a week for the first 2 weeks followed by thrice weekly administration for 12 weeks or more. ANA, TMA, AMA and anti-DNA antibody newly developed in 8, 1, 2 and 1 patient, respectively. Furthermore, we encountered some cases in which underlying autoimmune disorders were thought to be exacerbated by IFNs. It is important to pay sufficient attention to the development of autoimmune diseases in IFN therapy for chronic hepatitis C.

Alpha‐interferon therapy for chronic hepatitis B virus infection in children and Oriental patients

In summary, these four studies showed that alpha-IFN therapy alone produced sustained inhibition of HBV replication in a minority of Chinese adults with chronic HBV infection. The response was not improved by instituting treatment at an earlier age. The major reason for the poor response in Chinese patients is probably immune tolerance as a result of early exposure to HBV. The response in Chinese patients with elevated pre-treatment serum ALT levels, who presumably had ongoing endogenous immune lysis of infected hepatocytes, was significantly better than and comparable with that reported in Caucasian patients. Prednisone priming did not provide any additional advantage over therapy with IFN alone in patients with normal pre-treatment serum ALT levels, but appeared to have additional benefit in patients with elevated ALT levels.