干扰素联合利巴韦林治疗慢性丙型肝炎致甲状腺功能异常临床分析

目的探讨IFN联合利巴韦林(RBV)治疗CHC致甲状腺功能异常的临床特点。方法回顾性分析78例CHC患者应用干扰素联合RBV治疗过程中出现甲状腺功能异常的临床资料。78例患者随机分为重组人干扰素α2b(IFN-α2b)组58例,聚乙二醇化干扰素α-2a(Peg-IFN-α2a)组20例。结果 78例患者中,发生甲状腺功能异常(TD)者17例(21.79%),其中甲状腺功能亢进症5例,甲状腺功能减退症12例。78例患者的性别、基线HCV RNA载量、丙型肝炎病程、病毒应答时间、总疗程与TD发生无显著相关性,年龄、既往TD病史有显著相关性。78例患者中,有15例为一过性TD,仅2例终止干扰素治疗。两组患者导致TD的发生率分别为10%(2/20)和25.80%(15/58)。两组患者的年龄(χ2=4.974,P=0.026,OR=1.073)、既往TD病史(χ2=5.123,P=0.024,OR=16.569)与甲状腺疾病发生呈现正相关。出现TD时间主要集中在干扰素治疗后31~60天。结论 TD是干扰素治疗CHC中较常见的不良反应,特别是既往有TD病史者,多数TD为短暂性异常,应在密切监视下完成抗病毒疗程。     

Retreatment with interferon-alpha and ribavirin in primary interferon-alpha non-responders with chronic hepatitis C

BACKGROUND/AIMS: Combination therapy with interferon-alpha (IFN-alpha) plus ribavirin is more efficacious than IFN-alpha monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-alpha relapse. Only limited data are available in IFN-alpha non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-alpha-resistant chronic hepatitis C. METHODS: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-alpha-2a (3 x 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-alpha dose of 3 x 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. RESULTS: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-alpha dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). CONCLUSIONS: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-alpha non-responders. Higher IFN-alpha induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1.     

Consensus interferon and ribavirin for patients with chronic hepatitis C and failure of previous interferon-alpha therapy.

BACKGROUND: The efficacy of consensus interferon (CIFN), a synthetic IFN with optimised in vitro activity, was assessed in chronic hepatitis C virus (HCV) patients who had failed the pretreatment with interferon-alpha (IFNalpha) and ribavirin. METHODS: One hundred and three patients after non-response (n=69) or relapse (n=34) to IFNalpha+/-ribavirin were randomly assigned to high-dose induction (CIFN 27-->9 microg daily for 24 weeks, 9 microg t.i.w. for 24 weeks) or low-dose treatment (CIFN 18 microg t.i.w. for 12 weeks, 9 microg t.i.w. for 36 weeks); each with ribavirin 800 mg/day. Follow-up was 24 weeks. RESULTS: Non-responder patients treated with high-dose induction had higher early virological response rates (63% vs. 39%, P<0.05). This initial positive effect was lost during the last 24 weeks of treatment yielding sustained virological response (SVR) rates of 26% in both groups. Relapse patients revealed SVR in 70% and 38% in groups A and B (NS). Treatment was well tolerated with side effect-related preterm discontinuations in 8% and 5%. CONCLUSIONS: CIFN and ribavirin treatment induced considerable SVR rates in patients with non-response or relapse to IFNalpha+/-ribavirin. Viral elimination rates might be further increased by continuous daily administration of CIFN and weight-adjusted ribavirin dosing.     

Combination therapy with interferon-alpha and ribavirin in patients with dual hepatitis B and hepatitis C virus infection

BACKGROUND: Patients with dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infection have responded poorly to interferon (IFN) monotherapy. The purpose of the present paper was to assess the effect of combined IFN-alpha and ribavirin therapy in patients infected with both hepatitis B and C. METHODS: Thirty-six patients received 3 or 5 MU IFN-alpha-2b thrice weekly and oral ribavirin (800-1200 mg/day) for 24 weeks. All patients had positive hepatitis B surface antigen, antibody to HCV, and HCV-RNA. Before treatment, one patient had positive hepatitis B e antigen. Eighteen patients had positive HBV-DNA tested by Amplicor (Cobas Amplicor Monitor, Roche Diagnostics, Branchburg, NJ, USA), with a mean HBV-DNA level of 3.1 +/- 0.9 log copies/mL. Another 72 patients with HCV infection alone served as controls. RESULTS: Adverse events led to withdrawal in three patients receiving 5 MU IFN. Based on an intent-to-treat analysis, the biochemical response and serum HCV clearance rate at the end of 48 weeks follow up was similar in patients with dual infection and HCV infection alone (56% vs 72%; and 69% vs 71%, respectively). There was no significant difference in sustained HCV clearance rate between the 3-MU group (n = 13) and the 5-MU group (n = 23; 85% vs 61%). At the end of 48 weeks follow up, two (11%) of 18 pretreatment viremic patients had negative serum HBV-DNA (<200 copies/mL), while eight of those without pretreatment viremia had re-occurrence of HBV-DNA. CONCLUSIONS: Combination therapy with IFN-alpha and ribavirin was effective in achieving sustained HCV clearance in patients with dual HBV and HCV infection, comparable to those with hepatitis C infection alone. Combination therapy using 3 MU IFN-alpha seemed as effective as 5 MU, and was well tolerated in the study population. However, large-scale control trials are necessary to clarify these findings.     

Interferon-antibodies and the breakthrough phenomenon during ribavirin/interferon-alpha combination therapy and interferon-alpha monotherapy of patients with chronic hepatitis C.

BACKGROUND/AIMS: The significance of interferon antibodies with respect to response to treatment in patients with chronic hepatitis C treated with interferon-alpha (INF-alpha) remains a matter of debate. The influence of ribavirin on IFN-antibody formation in combination therapy with IFN-alpha has not yet been studied. Therefore we evaluated the relationship between IFN-antibodies and response to ribavirin/IFN-alpha combination therapy and IFN-alpha monotherapy. METHODS: We studied 169 patients with chronic hepatitis C who were treated either with IFN alpha 2a (6 MU, thrice weekly) alone or in combination with ribavirin (14 mg/kg per day) for twelve weeks. Thereafter, patients who achieved a virological response (HCV-RNA-negative) were treated with 3 MU IFN-alpha thrice weekly for another 40 weeks. IFN antibodies were analyzed and quantified by a double-antigen sandwich enzyme immunoassay (EIA). In 86 patients two neutralization assays--an antiviral neutralization assay as well as an antiproliferative neutralization assay--were performed in addition. The relationship of the development of IFN-antibodies with the virologically defined response to treatment was analyzed. RESULTS: Ribavirin did neither influence the prevalence nor the level of IFN-antibodies. The frequencies of IFN-antibody formation did not differ in the response groups. However, patients with breakthrough showed significantly higher IFN-antibody titers as compared to responder at end of treatment (median 1,336 BU/ml vs. 148 BU/ml; p = 0.018). Among the breakthrough patients those with IFN-antibodies showed the reappearance of HCV-RNA during therapy significantly earlier (median week 24) than those without IFN-antibodies (median week 32; p = 0.03). CONCLUSION: The addition of ribavirin to IFN-alpha does not influence the formation of IFN-antibodies. The development of high-titer IFN-antibodies during IFN-alpha or ribavirin/IFN-alpha therapy of patients with chronic hepatitis C may account for the early occurrence of breakthrough in some patients, while other mechanisms seem to be responsible for this phenomenon in the majority of the afflicted patients.     

Gastric autoimmune disorders in patients with chronic hepatitis C before,during and after interferon-alpha therapy

AIM: To explore the prevalence of autoimmune gastritis in chronic hepatitis C virus (HCV) patients and the influence of α-interferon (IFN) treatment on autoimmune gastritis.METHODS: We performed a prospective study on 189 patients with positive anti-HCV and viral RNA enrolled in a 12-month IFN protocol. We evaluated: a) the baseline prevalence of autoimmune gastritis, b) the impact of IFN treatment on development of biochemical signs of autoimmune gastritis (at 3, 6 and 22 months), c) the evolution after IFN withdrawal (22 months) in terms of anti-gastric-parietal-cell antibodies (APCA), gastrin, anti-thyroid, and anti-non-organ-specific antibodies. RESULTS: APCA positivity and 3-fold gastrin levels wered etected in 3 (1.6 %) and 9 (5 %) patients, respectively, at baseline, in 25 (13 %) and 31 (16 %) patients at the end of treatment (both P&lt;0.001, vs baseline), and in 7 (4 %) and 14 (7 %) patients 12 months after withdrawal (P=0.002 and P=0.01 respectively, vs baseline; P=not significant vs end of treabnent). The development of autoimmune gastritis was strictly associated with the presence of autoimmune thyroiditis (P =0.0001), no relationship was found with other markers of autoimmunity.CONCLUSION: In HCV patients, IFN frequently precipitates latent autoimmune gastritis, particularly in females. Following our 12-month protocol, the phenomenon generally regressed. Since APCA positivity and high gastrin levels are associated with the presence of antithyroid antibodies,development of autoimmune thyroiditis during IFN treatment may provide a surrogate preliminary indicator of possible autoimmune gastritis to limit the need for invasive examinations.     

Ischemic colitis during pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.

Rare cases of ischemic colitis associated with interferon-alpha (IFN-alpha) treatment for chronic hepatitis C (HCV) infection and metastatic cancer have been reported. The present study describes the first case of ischemic colitis attributable to pegylated IFN-alpha and ribavirin combination therapy in an HCV-infected patient after 34 weeks of treatment. The clinical presentation, endoscopic appearance and histopathology of the colon were consistent with ischemic colitis, and the patient's symptoms rapidly resolved with cessation of therapy. The association between the therapy and the pathogenesis of ischemic colitis is unclear, but immunoregulatory, vasospastic and procoagulant mechanisms have been proposed. Physicians should be aware of this complication, and should consider it in any HCV-infected patient taking pegylated IFN-alpha and ribavirin who develops abdominal discomfort and gastrointestinal bleeding.     

Th1 response during ribavirin and interferon-alpha combination therapy in chronic hepatitis C.

Ribavirin and interferon-alpha induce Th1 polarization of human CD4+ T cells. The study was conducted to investigate the whether cellular immune response during ribavirin/interferon-alpha therapy is associated with viral eradication by examining mRNA expression of molecules relevant to Th1 and Th2 polarization in CD4+ cells of 13 patients with chronic hepatitis C (seven patients with sustained viral response and six with transient response). Peripheral CD4+ T lymphocytes at 0, 4 and 24 weeks of treatment were tested. There were no significant differences in the mRNA levels at each point of time of the treatment between patients with sustained viral response and those with transient response. The percent increase in mRNA level of the IL-12R beta2 chain from the baseline to the end of the treatment was significantly higher in patients with sustained viral response (15.3+/-6.1%) than in those with transient response (-1.6+/-4.7%, p<0.05). There was no significant difference in percent changes in level of IL-12R beta1 chain mRNA between the two groups. In conclusion, the results of this study indicate that the increase of Th1 response is related to the inflammatory activity in the liver and possibly to ribavirin and interferon-alpha therapy. It is also suggested that the measurement of Th1 response has the potential to distinguish patients with relapse from those with sustained virus response.     

Efficacy and safety of combination therapy with interferon-alpha2b and ribavirin for chronic hepatitis C in HIV-infected patients

OBJECTIVES: To evaluate the efficacy and safety of a combination therapy of interferon-alpha2b (IFN) and ribavirin for the treatment of chronic hepatitis C in HIV-seropositive patients. DESIGN: Open prospective trial. METHODS: Twenty patients co-infected with hepatitis C virus (HCV) and HIV, with a mean CD4 cell count of 350 +/- 153 x 10(6)/l were treated with IFN (3 MU three times per week) in combination with ribavirin (500 mg or 600 mg twice a day) for 6 months. Tolerance and efficacy were monitored at weeks 12 (month 3) and 24 (month 6). The primary endpoint was a complete virological response, as defined by the lack of detectable HCV RNA in serum. RESULTS: Baseline values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were 121 +/- 72 IU/l and 75 +/- 67 IU/l, respectively. The total Knodell score was 10.4 +/- 2.4, with nine patients showing histological evidence of active cirrhosis (45%). All patients exhibited circulating HCV RNA. The treatment was well tolerated, with no impact on the course of HIV infection. After 6 months of combination therapy with IFN and ribavirin, 10 patients (50%) exhibited no further detectable HCV RNA viraemia, seven of whom achieved undetectable viraemia at month 3. Levels of ALT and AST decreased after 6 months of treatment from a mean of 121 +/- 72 to 51 +/- 40 IU/l and from a mean of 129 +/- 58 IU/l to 68 +/- 61 IU/l, respectively (P < 0.0002 and P < 0.0001). CONCLUSION: Our results indicate that combination therapy with IFN and ribavirin is effective in 50% of cases in clearing serum HCV RNA and may thus provide effective means of therapy in HIV-HCV-coinfected patients as initial treatment or in patients who have previously failed IFN monotherapy.     

Thyroid dysfunction in hepatitis C individuals treated with interferon-alpha and ribavirin: a review

Hepatitis C (HCV) is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. Several extrahepatic diseases have been associated with chronic HCV infection, and in most cases appear to be directly related to the viral infection. Thyroid disorders are common in patients with chronic HCV. Some patients with chronic hepatitis C experience thyroid problems, and thyroid dysfunction may also be a side effect of interferon-based treatment. The principal risk factor for developing thyroid disease in the course of antiviral therapy is the previous positivity for anti-thyroid antibodies (anti-thyroid peroxidase) especially in older women. Screening for autoantibodies and serum thyroid-stimulating hormone is recommended before, during and after interferon-alpha treatment, and patients should be informed of the risk of thyroid dysfunction. This review includes a summary of thyroid disease associated with chronic HCV infection, interferon-alpha and ribavirin for treatment of HCV and potential to induce thyroid dysfunction.     

Thyroid disorders in chronic hepatitis C

PURPOSE: To explore the association of hepatitis C virus (HCV) infection with thyroid disorders. METHODS: We investigated the prevalence of thyroid disorders in 630 consecutive patients with chronic hepatitis due to HCV infection; all patients were free of cirrhosis and hepatocarcinoma, and were not on interferon treatment. Also included were a control group of 389 subjects from an iodine-deficient area, another control group of 268 persons living in an area of iodine sufficiency, and 86 patients >40 years of age with chronic hepatitis B. Levels of thyroid-stimulating hormone (TSH), free thyroxine (T(4)), and triiodothyronine (T(3)), as well as anti-thyroglobulin and anti-thyroid peroxidase antibodies, were measured. RESULTS: Mean TSH levels were higher (P = 0.001), and free T(3) and free T(4) levels were lower (P <0.0001), in patients with chronic hepatitis C than in all other groups. Patients with chronic hepatitis C were more likely to have hypothyroidism (13% [n = 82]), anti-thyroglobulin antibodies (17% [n = 108]), and anti-thyroid peroxidase antibodies (21% [n = 132]) than were any of the other groups. CONCLUSION: Both hypothyroidism and thyroid autoimmunity are more common in patients with chronic hepatitis C-even in the absence of cirrhosis, hepatocellular carcinoma, or interferon treatment-than in normal controls or those with chronic hepatitis B infection.     

Pegylated interferon plus ribavirin combination therapy for chronic hepatitis C in patients with congenital coagulation disorders

Chronic hepatitis C (CHC) and end-stage liver disease are becoming an increasingly common cause of mortality in patients with congenital bleeding disorders, especially in the HIV-coinfected group. Combination of pegylated interferon (Peg-IFN) and ribavirin has recently become the treatment of choice for CHC. In this study, we evaluated the safety and efficacy of combination therapy with Peg-IFN plus ribavirin for the treatment of CHC in human immunodeficiency virus (HIV)- and HIV+ patients with congenital bleeding disorders. Between 2000 and 2004, 50 (18-68 years old) patients with CHC (19 HIV+) from two hemophilia centers were included in the study. They were treated with weekly subcutaneous administration of Peg-INF-alpha combined with 800-1,200 mg ribavirin daily, for 24-48 weeks depending on viral genotype. Response was evaluated at weeks 12, 24, 48 (end of treatment response) and 72 had sustained virological response). Overall, 22/50 patients (43.8%) had end of treatment response and 20/50 (40%) sustained virological response. HIV- patients responded similarly to the general population (58.1%), while HIV+ patients had very low response rates (10.5%). The high rate of discontinuation (36.9%) as a result of side effects contributed to the observed low response rate in the HIV+ group. The only factor strongly associated with sustained virological response in the HIV- patients was the reduction of HCV RNA at 12 weeks (p = 0.001). Patients with viral genotypes other than 1 had higher SVR rates, but this was not found to be statistically significant. Peg-INF plus ribavirin is safe for the treatment of CHC monoinfected patients with inherited bleeding disorders, with similar response rates to nonhemophiliacs. On the contrary, in HIV coinfected hemophilic patients under highly active antiretroviral therapy it is associated with severe toxicity and very poor sustained virological response rates. Careful evaluation and several considerations are needed before starting treatment in this population.     

Pilot study of interferon-alpha high-dose induction therapy in combination with ribavirin plus amantadine for nonresponder patients with chronic hepatitis C

Ribavirin plus interferon-alpha (IFN alpha) combination has led to a marked advance in the treatment of IFN alpha-naive or relapser patients with chronic hepatitis C but was shown to be only marginally effective in IFN alpha-nonresponders. We therefore conducted a pilot study to see whether an intensified treatment protocol might be more effective in inducing a virological response in patients who had not responded virologically to previous IFN alpha monotherapy. 14 nonresponder patients with histologically proven chronic hepatitis C were included in the study. Patients received 9 MU IFN alpha-2a daily for one week followed by 9 MU IFN alpha every second day for further 5 weeks. With the beginning of the seventh week, patients were treated with 6 MU IFN alpha thrice in week (tiw) for a period of 6 weeks (until week 12). IFN alpha was continued up to 48 weeks at a dose of 3 MU IFN alpha tiw. Ribavirin (1000-1200 mg/day) and amantadine sulphate (200 mg/day) was given orally for 48 weeks. One patient discontinued therapy after first IFN alpha injection and one other patient after 12 weeks of therapy because of side effects. The remaining 12 patients completed treatment according to the protocol. An initial virological response at week 24 was achieved in 2 of the 14 patients (14%) and both patients remained HCV RNA negative at the end of treatment. However, both patients relapsed 4 weeks after completion of therapy, and therefore none of the patients achieved a virological sustained response. Viral dynamics studies showed a marked decline in hepatitis C viremia during the first 6 weeks of high-dose IFN alpha. After IFN alpha dose reduction, however, viremia stabilized or increased in most patients. These data indicate, that even triple therapy with high-dose IFN alpha plus ribavirin and amantadine fails to improve significantly the response rates in IFN alpha-nonresponders.     

Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-α therapy

BACKGROUND AND AIMS Hepatitis C virus is involved in the induction of autoimmunity and interferon can also induce hepatic and non-hepatic autoimmune reactions. This study assessed the prevalence of thyroid autoantibodies and autoimmune thyroid disorders in patients with chronic hepatitis C before and during interferon therapy. PATIENTS AND METHODS We studied prospectively 207 patients positive for anti-HCV and viral RNA. One hundred and forty-four of them received a therapeutic trial of one year with interferon-α. Free thyroxine, TSH and autoantibodies to thyroglobulin and thyroid microsomes were systematically tested at entry and at weeks 12 and 24 in both untreated and treated patients. RESULTS Sixteen of the 207 patients (7.7%) had thyroid dysfunction, including positive antithyroid antibodies in 14 (6.7%) and hypothyroidism in 10 (4.8%) prior to interferon therapy. In addition, during pretreatment evaluation one patient developed clinical hyperthyroidism after transient subclinical hypothyroidism and another had subclinical hyperthyroidism. Prevalences of positive antithyroid antibodies and hypothyroidism were significantly higher in women (14.7 and 10.5%, respectively, vs 0% in men, P < 0.01) and were directly associated with increasing age (P < 0.01). The incidence of thyroid dysfunction was also significantly higher in patients with other autoantibodies such as anti-nuclear (ANA) (P < 0.01). A trial with interferon was initiated in 144 patients and 8 of 142 (5.6%) without previous thyroid abnormalities developed thyroid dysfunction, including positive antithyroid antibodies in 7 (4.9%) and hypothyroidism in 4 (2.8%) with a prevalence again significantly higher in women (12.7 and 8.3%, respectively, vs 1% in men, P < 0.01) and also directly related to increasing age (P < 0.01). An association was found between the development of thyroid dysfunction during interferon therapy and the presence of other autoantibodies, including ANA, anti-DNA and anti-Sjögren’s antibodies (P < 0.01), as well as with the induction of autoimmune hepatitis and Sjögren's syndrome (P < 0.01 and < 0.05 respectively). Thyroid abnormalities were reversed in all patients when interferon therapy was discontinued. CONCLUSIONS No significant association was found between chronic hepatitis C and the presence of thyroid autoimmunity in female patients. On the contrary, interferon therapy induced antithyroid autoantibodies and thyroid dysfunction de novo in patients with chronic hepatitis C without pre-existing thyroid abnormalities. Thyroid dysfunction secondary to interferon was reversible after discontinuation of therapy.     

Combination therapy with interferon-alpha(2b), ribavirin,and amantadine in chronic hepatitis C nonresponders to interferon and ribavirin

Standard therapies for the treatment of hepatitis C are ineffective in almost 50% of patients. Amantadine is an antiviral agent that may have activity against hepatitis C virus. In this pilot study, we evaluated the efficacy of a combination of interferon, ribavirin, and amantadine in patients with chronic hepatitis C who had previously failed 6–12 months of treatment with interferon and ribavirin. In this prospective open-label study, 23 patients were treated with a combination of interferon-_2b 3 million units subcutaneously three times per week, ribavirin 1000–1200 mg daily, and amantadine 100 mg twice daily for 6–12 months. Treatment was discontinued at 6 months if the patients had detectable HCV RNA by PCR. All patients were followed for 6 months after the completion of treatment. At the end of treatment, the biochemical response was 47% and the virological response was 30%. However, the rate of sustained virological response was only 13% (3/23). There were no unexpected side effects with triple therapy. In conclusion, triple therapy with interferon, ribavirin and amantadine resulted in a low sustained viral clearance in chronic hepatitis C patients who had previously failed interferon and ribavirin combination therapy.     

Long-term efficacy of combination therapy with interferon-alpha 2b and ribavirin for severe chronic hepatitis C in HIV-infected patients.

BACKGROUND: We have assessed the long-term efficacy and safety of a combination therapy of interferon alpha-2b (IFN) and ribavirin (RBV) for the treatment of severe chronic hepatitis C in co-infected HIV-seropositive patients in an open prospective study. METHODS: Fifty-one patients were treated for 12 months. Mean baseline CD4 cell count, alanine aminotransferase and aspartate aminotransferase were 412 +/- 232 x 106/l, 113 +/- 75 IU/l and 111 +/- 84 IU/l respectively. The mean Knodell score was 11.5 +/- 2.1 with 28 patients (55%) exhibiting histological evidence of active cirrhosis. RESULTS: Fifteen (29%) patients discontinued the treatment prematurely because of adverse events. An end of treatment response (ETR) as defined by the lack of detectable hepatitis C virus (HCV) RNA in plasma at the end of treatment was achieved in 15 patients (29%). A sustained virological response (SVR), defined by the lack of detectable HCV RNA in plasma 6 months after completion of combination therapy, was achieved in 11 patients (21%). The HCV genotype 3a was associated with ETR and SVR (P = 0.002 and P = 0.003, respectively). HCV viraemia at baseline was lower in patients who achieved SVR and ETR than in those who did not (6.7 +/- 7.8 versus 24 +/- 26.7 x 10(6) genome equivalents/ml, P = 0.03 and 14.3 +/- 28.7 versus 22.5 +/- 23, P = 0.05, respectively). CONCLUSION: Our results indicate that combination therapy with IFN and RBV is effective in approximately 20% of co-infected patients with severe liver disease.     

High initial dose combination regimen with interferon-alpha and ribavirin in chronic hepatitis C

BACKGROUND/AIMS: Combination of interferon-alpha and ribavirin becomes the antiviral therapy of choice for chronic hepatitis C. The aim of this trial was to assess the efficacy of two combination treatment strategies: standard regimen Interferon-alpha 3 MU three times per week (group A) and initial high dose Interferon 6 MU daily for 2 weeks followed by intermittent administration 3 MU three times per week (group B), plus Ribavirin in naive and relapsed patients with chronic hepatitis C. METHODOLOGY: Twenty-four patients (group A, 6; group B, 18) received medication for median 6 months (range, 5-12) and followed for 6 months. Primary end-point of therapy was a sustained virologic response. Statistical analysis was performed with a t test or non-parametric Mann-Whitney and chi-square test. RESULTS: At the end of the follow-up the overall sustained response rate was 42%: 6 of 18 (33.3%) patients with induction and 4 of 6 (66.6%) with standard regimen. Patients with sustained virologic response received higher interferon dose (423.7 +/- 102.2 MU) at extended duration of therapy (9.8 +/- 2.9 months) versus patients with non-sustained response (p < 0.05). The difference in sustained response rate in both treatment regimens was nonsignificant. CONCLUSIONS: High initial dose therapy does not enhance virologic response, compared to standard combination regimen.     

Prolonged therapy of chronic hepatitis C with ribavirin

Summary. Therapy with ribavirin for 6–12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000–1200mg of ribavirin daily for 24 months. Serum aminotranferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long-term side-effects.