Randomized trial of three different regimens for 24 weeks for re-treatment of chronic hepatitis C patients who failed to respond to interferon-alpha monotherapy in Taiwan.

With the favorable result of interferon (IFN)-ribavirin combination therapy for 24 weeks among naive Taiwanese chronic hepatitis C (CHC) patients, the optimal regimens of re-treatment for CHC patients who failed initial IFN monotherapy is not well-established. The study evaluated the effectiveness of re-treatment for 24 weeks with 3 different regimens and predictors for sustained virological response (SVR). METHODS: Total 120 Taiwanese CHC patients (81 males, 70 relapsers, mean age: 48.6 years) who failed initial IFN monotherapy were enrolled. They were assigned randomly (with a ratio of 1:1:2) to receive one of the three regimens for re-treatment for 24 weeks; group A: IFN 6 million units (MU) monotherapy (N=30), group B: combination therapy with ribavirin and IFN 3 MU (N=30) or group C: combination therapy with ribavirin and IFN 6 MU (N=60). The intention-to-treat rate of sustained virological response (SVR) was 38.3%. The SVR rate in group C (53.3%) was significantly higher than group A (16.7%, P<0.005) and group B (30%, P<0.05). Drop-out rates were similar between the three groups. Patients achieving SVR had significant improvement histologically. Hepatitis C virus (HCV) genotype non-1b infection, lower pretreatment HCV RNA levels, combined with ribavirin and with higher IFN dose, and relapsers were independent predictors for SVR. CONCLUSION: We concluded that more than one-third Taiwanese CHC patients achieved SVR after 24 weeks re-treatment and combination therapy, especially with higher dose of IFN, yielded higher efficacy.     

Daily dose of interferon alpha-2b and ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection: a randomised controlled study

OBJECTIVE: The treatment of patients with hepatitis C virus (HCV) genotype 1 infection remains disappointing. METHODS: In 1999, we started a multicentre study comparing two regimens of recombinant interferon (IFN) alpha-2b plus ribavirin. Group A (90 patients) received ribavirin plus IFN alpha-2b 5 MU/day for 1 month (induction therapy) followed by IFN alpha-2b 5 MU thrice weekly for 5 months. Group B (85 patients) received ribavirin plus IFN alpha-2b 5 MU thrice weekly for 6 months. Responders in both arms received IFN alpha-2b 3 MU thrice weekly for a further 6 months. A follow-up evaluation was performed at 18 months. RESULTS: One hundred and seventy-five consecutive treatment-naive patients with HCV genotype 1 infection were enrolled in the study. A sustained virological response (SVR) was obtained in 51 (29%) patients: 28 in group A (31%) and 23 in group B (27%). HCV-RNA clearance was greater at 3 months among patients who received induction therapy (57 vs 39%; p < 0.02). Age, sex, and initial viral load did not influence the achievement of a SVR. HCV clearance at the end of the study was lower in cirrhotic patients (3/26 vs 48/149; p < 0.05). The only SVR in patients with cirrhosis occurred in those from group A (p < 0.05). Both regimens were well tolerated. CONCLUSIONS: This study confirms the low rate of SVR in treatment-naive patients with HCV genotype 1 infection treated with IFN alpha-2b plus ribavirin. A 4-week induction regimen was slightly superior to standard IFN alpha-2b plus ribavirin. Although the number of patients with cirrhosis was low, induction therapy seemed to be more effective in cirrhotics. Given its safety and tolerability, the induction regimen evaluated here may be a therapeutic option in treatment-naive patients with HCV genotype 1 infection.     

Peginterferon alpha-2a (40 KD) plus ribavirin for the treatment of chronic hepatitis C in Japanese patients

Background: The efficacy and safety of peginterferon alpha‐2a (40 KD) (peg‐IFNα‐2a) plus ribavirin has not been reported for Japanese patients with chronic hepatitis C. The aim of this study was to evaluate this combination in treatment‐naïve patients and in non‐responders or relapsers to interferon monotherapy. Methods: Overall, 201 treatment‐naïve patients with hepatitis C virus (HCV) genotype‐1b were randomly assigned to 180 µg peg‐IFNα‐2a once‐weekly plus ribavirin 600–1000 mg/day or peg‐IFNα‐2a plus placebo for 48 weeks. Additionally, peg‐IFNα‐2a plus ribavirin was administered for 48 weeks to 100 non‐responders or relapsers (85% genotype‐1) to previous interferon monotherapy. Results: A sustained virological response (SVR) was attained among significantly more treatment‐naïve patients receiving combination therapy than monotherapy (61% vs 26%, P < 0.001). For patients with high baseline HCV RNA, the SVR rate was 59% with peg‐IFNα‐2a plus ribavirin versus 24% with peg‐IFNα‐2a monotherapy. Among non‐responders or relapsers to previous interferon monotherapy, 54% attained an SVR. Adverse events were generally mild, and discontinuations rates due to adverse events or laboratory abnormalities were low. Conclusion: In Japanese patients, peg‐IFNα‐2a plus ribavirin provided significant improvement in SVR rates compared with peg‐IFNα‐2a alone in treatment‐naïve patients, and was effective as re‐treatment for non‐responders or relapsers to previous treatment with interferon monotherapy.     

Retreatment for 24 vs 48 weeks with interferon-alpha2b plus ribavirin of chronic hepatitis C patients who relapsed or did not respond to interferon alone

We assessed the efficacy of interferon (IFN) plus ribavirin over 24 or 48 weeks for the retreatment of patients with chronic hepatitis C who had relapsed or did not respond to a previous course of IFN. One-hundred and twenty patients (69 non-responders and 51 relapsers) were randomly assigned to receive IFN-alpha2b (3 million units thrice weekly) plus ribavirin (1,000-1,200 mg per day) for 24 weeks (group A: 58 patients) or 48 weeks (group B: 62 patients). Treatment was discontinued at week 12 if the alanine aminotransferase (ALT) level remained elevated. The rate of sustained response was 15.5% in group A and 37.1% in group B (P = 0.013). Relapsers treated for 48 weeks had a sustained response rate of 66.6% compared with a sustained response rate of only 25% in those treated for 24 weeks (P = 0.004). Moreover, a sustained response was seen in 14.3% of non-responders treated for 48 weeks and in 8.8% of those treated for 24 weeks (P = 0.71). Fifty-three per cent of patients with a normal ALT level and undetectable hepatitis C virus (HCV) RNA at week 12 had a sustained response compared with 14% of those who were HCV RNA positive at week 12 (P < 0.001). Independent predictive factors of sustained response were: therapy for 48 weeks (P = 0.0026), relapse after IFN treatment (P = 0.0006), loss of HCV RNA at week 12 (P = 0.0008) and HCV genotype non-1 (P = 0.024). Hence, in patients with chronic hepatitis C who failed to respond to a previous course of IFN monotherapy, combination therapy with IFN plus ribavirin for 48 weeks seems to be more effective than IFN plus ribavirin for 24 weeks.     

Treatment effects and predictors of a 24-week course of interferon alpha-2b plus ribavirin combination therapy for patients with chronic hepatitis C

BACKGROUND AND AIMS: In chronic hepatitis C patients with genotype 1b and a high viral load, the sustained virological response (SVR) rate remained as low as 2-3% with conventional interferon (IFN) monotherapy, but improved to more than 20% with IFN alpha-2b plus ribavirin combination therapy. This study examined the therapeutic effects and predictors of this combination therapy. METHODS: Subjects were 105 patients with chronic hepatitis C (73 males, 32 females) with a median age of 53 years (range 19-70 years). Seventy-two patients had genotype lb and 33 patients had genotype 2 (2a or 2b). Six million units (MU) or 10 MU of IFN alpha-2b was administered by intramuscular injection six times a week for the first 2 weeks, and the same amount of IFN was administered three times a week for the following 22 weeks. During the IFN administration period, 600-800 mg of oral ribavirin was administered daily. Patients who were hepatitis C virus (HCV)-RNA negative 24 weeks after the completion of administration were defined as SVR. RESULTS: The overall SVR rate was 39%; 22.2% for the genotype 1b group and 75.8% for the genotype 2 group, and the difference between the groups was significant (P < 0.0001). Multivariate logistic regression analysis indicated that the factors that contributed to SVR include genotype 2, age (younger than 53 years), and an increase in Th2 measured by flow cytometry before and 4 weeks after start of treatment. CONCLUSIONS: The overall SVR rate of IFN alpha-2b plus ribavirin combination therapy for 24 weeks was 39%, and contributing factors for SVR rate include genotype 2, age younger than 53 years and elevated Th2.     

Therapeutic modalities in hepatitis C: challenges and development

Our understanding of the pathogenicity of hepatitis C virus (HCV) is based on patients infected chronically for >20 years. The lack of a suitable animal model, the narrow host range of the virus, and the protracted onset of liver disease induced by HCV have hampered advances in treatment. In spite of these problems, we identified patient and viral characteristics that predict responses to current therapies, including HCV genotype, viral load, body weight, age, liver histology, co-infection with HIV and treatment adherence and tolerance. Interferon (IFN) alpha was the first therapy for chronic HCV infection. The combination of IFN plus ribavirin increases sustained virological response rates compared with IFN alone. Two pegylated IFNs have been developed and are widely approved for the treatment of chronic hepatitis C: peginterferon alpha-2a (40 KD), and pegylated IFN alpha-2b (12 KD). These products have reduced systemic clearance, prolonged half-lives and reduced antigenicity compared with conventional IFN. The reduced clearance results in sustained plasma levels of the drug and allows for once-weekly dosing. Pegylated IFN alpha-2b (12 KD) has a small, linear polyethylene glycol (PEG) moiety and has an intermediate duration of activity; peginterferon alpha-2a (40 KD) incorporates a large, branched-chain PEG moiety and has a longer half-life than both conventional IFN alpha and pegylated IFN alpha-2b (12 KD). The combination of a pegylated IFN plus ribavirin significantly increases sustained virological response rates compared with conventional IFN plus ribavirin in patients with chronic hepatitis C and is now recognized as the standard of care for these patients.     

Therapeutic effects of pegylated interferon plus ribavirin in chronic hepatitis C patients with occult hepatitis B virus dual infection

Background and Aim: Occult hepatitis B virus (HBV) infection is defined by the detectable serum HBV–DNA in HBV surface antigen‐negative patients. This retrospective study aims to evaluate the therapeutic effects of combined pegylated interferon (PEG–IFN) plus ribavirin (RBV) in patients with concurrent occult HBV/hepatitis C virus (HCV) dual infection. Methods: In total, 126 consecutive chronic hepatitis C (CHC) patients who received combined PEG–IFN and RBV therapy were included. Patients were divided into the occult HBV/HCV dual infection group or the HCV‐monoinfected group according to whether or not they had the detectable serum HBV–DNA. The biochemical and virological responses to combined therapy were compared between these two groups. Serum HCV‐RNA and HBV–DNA were checked before treatment, at the end of treatment as well as at 6‐ and 12‐months' follow up in the occult HBV/HCV group. Result: Six patients were seropositive for HBV–DNA and were included in the occult HBV/HCV dual infection group. There were no statistical differences in the biochemical and virological responses to combined therapy between these two groups. Undetectable serum HBV–DNA was noted at the end of the treatment and the 6‐ and 12‐months' follow up in patients with occult HBV/HCV dual infection. Conclusion: Occult HBV infection in CHC patients is rare. The biochemical and virological responses to combined PEG–IFN and RBV therapy might be similar in CHC patients with or without occult HBV infection. The serum HBV–DNA level was low in patients with occult HBV/HCV dual infection who responded to combined therapy.     

Twenty-four weeks of interferon alpha-2b in combination with ribavirin for Japanese hepatitis C patients: sufficient treatment period for patients with genotype 2 but not for patients with genotype 1.

BACKGROUND: Hepatitis C virus (HCV) RNA titer and HCV genotype are two major determinants of the outcome of interferon (IFN) monotherapy. To clarify the usefulness of combination therapy with IFN and ribavirin in Japanese hepatitis C patients, we treated patients with a relatively high dose of IFN in combination with ribavirin for 24 weeks and examined the effects in relation to the viral parameters. METHODS: Two hundred and ninety-five patients were enrolled in the study. The patients received either 6 or 10 million units (MU) of interferon alpha-2b every day for 2 weeks and then three times a week for 22 weeks with a daily dose of either 600 or 800 mg of ribavirin. The treatment response and safety of this treatment were examined. RESULTS: The sustained virologic response (SVR) rates were 26.8% in genotype 1 and 76.5% in genotype 2 (P < 0.001), and 36.1% with the 6 MU group and 45.8% with the 10 MU group (P = 0.09). Multivariate analysis indicated that SVR was associated with genotype 2, HCV RNA <500 kilointernational unit/ml (kIU/ml), and HCV RNA undetectability at week 8 of treatment. CONCLUSION: Our current study showed that a 24-week course of IFN plus ribavirin combination therapy was effective with respect to virologic response in Japanese hepatitis C patients, particularly in patients with HCV genotype 2.     

Triple therapy of initial high-dose interferon with ribavirin and amantadine for patients with chronic hepatitis C

Aims: We previously reported the potential effect of combination therapy of an initial high‐dose interferon (IFN) and amantadine on the eradication of HCV‐RNA in patients with chronic hepatitis C. The additive effects of amantadine on interferon and ribavirin combination therapy remain controversial. In this study we investigated the efficacy of initial high‐dose IFN with ribavirin and amantadine on the virological response in patients with chronic hepatitis C with a high viral load of genotype 1b. Methods: Twenty‐two patients with high viral loads of genotype 1b hepatitis C virus were enrolled in this pilot study. Patients were administered IFN‐beta for four weeks and then IFN‐alpha2b for 22 weeks with daily oral administration of ribavirin and amantadine. Results: A sustained virological response (SVR) was shown in 31.8% (seven of 22 patients). With the naïve patients, the SVR rate was 21.4% (three of 14 patients). In patients who could not eradicate HCV‐RNA by previous IFN monotherapy, the SVR rate was 50% (four of eight patients). Conclusion: Triple therapy with an initial high dose of IFN with ribavirin and amantadine may be effective, especially for chronic hepatitis C IFN‐retreatment patients with a high viral load of genotype 1b.     

Effect of lactoferrin in patients with chronic hepatitis C: combination therapy with interferon and ribavirin

OBJECTIVES: Lactoferrin has been reported to inhibit hepatitis C virus (HCV) infection in cultured human hepatocytes and HCV viremia in patients with chronic hepatitis C (CHC). The aim of this study was to evaluate the effect of combined triple therapy of lactoferrin, interferon and ribavirin in patients with CHC. METHODS: A total of 111 Japanese patients with CHC were randomly assigned to a lactoferrin group (n = 50) and a control group (n = 61). The lactoferrin group was treated with lactoferrin for 8 weeks and then with lactoferrin, interferon and ribavirin for 24 weeks; the control group was treated with interferon and ribavirin for 24 weeks. Serum anti-lactoferrin antibody, clinical and laboratory measurement were determined. RESULTS: The mean HCV RNA titer significantly decreased at the end of lactoferrin monotherapy. Sustained virological response to therapy was significantly higher (P < 0.05) in the lactoferrin responder group (55%) than in the control group (18%). CONCLUSIONS: The results show that the decrease in HCV RNA titer by lactoferrin monotherapy contributes to the effectiveness of the combined therapy of interferon and ribavirin in patients with CHC. Lactoferrin is a potential useful adjunct treatment for patients with CHC.     

Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan

Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated, and produced a higher response rate especially in genotype 1 infections. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. A total of 153 patients with biopsy-proven chronic hepatitis C were randomly assigned to receive either weekly injection of peginterferon alpha-2b 1.5 mcg/kg plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group, n = 76) or 3 MU of interferon alpha-2b t.i.w. plus ribavirin (IFN group, n = 77) for 24 weeks. Sustained virological response (SVR) was defined as the sustained disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Baseline demographic, viral and histological characteristics were comparable between the two groups. Using an intent-to-treat analysis, HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG-IFN rather than IFN (65.8%vs 41.0%, P = 0.019), but no difference was found in genotype non-1 patients (PEG vs IFN: 68.4%vs 86.8%, P = 0.060). Genotype 1 patients (28.6%) in the PEG-IFN group relapsed, as compared with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early virological response at week 12 of therapy and genotype non-1 were significant predictors to SVR. As compared with the IFN group, patients receiving PEG-IFN had a significantly higher rate of discontinuation, dose reduction, fever, headache, insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C Chinese patient, PEG-IFNalpha2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for genotype non-1 chronic hepatitis C Chinese patients. However, a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG-IFNalpha2b ribavirin.     

Impaired ability of interferon-alpha-primed dendritic cells to stimulate Th1-type CD4 T-cell response in chronic hepatitis C virus infection

In interferon-alpha (IFN-alpha)/ribavirin combination therapy for chronic hepatitis C (CHC), an enhanced T helper 1 (Th1) response is essential for the eradication of hepatitis C virus (HCV). We aimed to elucidate the role of IFN-alpha or IFN-alpha/ribavirin in dendritic cell (DC) ability to induce Th1 response in HCV infection. We generated monocyte-derived DC from 20 CHC patients and 15 normal subjects driven by granulocyte-macrophage colony-stimulating factor and interleukin 4 (IL-4) without IFN-alpha (GM/4-DC), with IFN-alpha (IFN-DC), with ribavirin (R-DC) or with IFN-alpha/ribavirin (IFN/R-DC) and compared their phenotypes and functions between the groups. We also compared them in 14 CHC patients between who subsequently attained sustained virological response (SVR) and who did not (non-SVR) by 24 weeks of IFN-alpha/ribavirin therapy. Compared with GM/4-DC, IFN-DC displayed higher CD86 expression, but lesser ability to secrete IL-10 and were more potent to prime CD4(+) T cells to secrete IFN-gamma and IL-2. Such differences were more significant in healthy subjects than in CHC patients. No additive effect of ribavirin was observed in DC phenotypes and functions in vitro either which was used alone or in combined with IFN-alpha. However, in the SVR patients, an ability of IFN/R-DC to prime T cells to secrete IFN-gamma and IL-2 was higher than those of IFN-DC and those of IFN/R-DC in the non-SVR group, respectively. In conclusion, DC from CHC patients are impaired in the ability to drive Th1 in response to IFN-alpha. Such DC impairment is restored in vitro by the addition of ribavirin in not all but some patients who cleared HCV by the combination therapy.     

Daily or three times per week interferon alpha-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C not responding to previous interferon alone

BACKGROUND/AIMS: We compared the efficacy and safety of the combined therapy of daily interferon alpha-2b and ribavirin with those of interferon alpha-2b three times per week alone or in combination with ribavirin in non-responder patients with hepatitis C virus (HCV) infection.METHODS: A total of 376 patients were randomly assigned to receive interferon alpha-2b (6 MU three times per week for 24 weeks followed by 3 MU three times per week for 24 weeks) alone (group A) or in combination with ribavirin for 48 weeks (group B), or daily interferon alpha-2b (3 MU per day for 24 weeks followed by 3 MU three times per week for 24 weeks) and ribavirin (group C).RESULTS: After 24 weeks of therapy, HCV RNA was undetectable in 11.7, 24.0, and 37.8% for groups A, B, and C, respectively. Sustained virological response was more frequent in patients who received combination therapy with three times weekly interferon (20.9%) or daily interferon (26.0%) than in patients who received interferon alone (5.8%) (P<0.001). The predictive HCV parameters for sustained response were a low viral load on day 7 and a negative HCV RNA on week 12.CONCLUSIONS: In conclusion, in non-responder patients with chronic hepatitis C, virological response with daily interferon and ribavirin, compared to interferon monotherapy, was significantly improved during treatment, although sustained virological response was similar for both combination therapies with ribavirin and three times a week or daily interferon.     

Kinetics of hepatitis C virus RNA load during pegylated interferon plus ribavirin therapy in Treatment-naive Chinese patients

BACKGROUND/AIMS: To investigate the viral kinetics of Chinese CHC patients received pegylated interferon plus ribavirin and examine the impact of HCV genotypes and severity of liver disease. METHODOLOGY: 65 treatment-naove CHC patients who finished a 24-week therapy with peginterferon (alpha-2b (1.5 mcg/kg/week) plus ribavirin (1000-1200 mg /day) and 24 weeks of follow-up were enrolled. Hepatic fibrosis was graded by the METAVIR scoring system. Serum quantitative HCV RNA was determined by Versant HCV RNA 3.0 assay (Bayer Inc.). RESULTS: Genotype non-1 patients responded quickly and a higher percentage of them achieved undetectable HCV RNA (< 615 IU/mL) at week 4 compared with genotype 1 patients (93% vs. 69%, p = 0.018). Degree of hepatic fibrosis significantly affected end-of-treatment and sustained response (SVR). For patients who did not achieve early virological response (EVR), the negative predictive value for SVR was 100%. In genotype 1 patients, undetectable HCV RNA by week 4 was a good marker to predict treatment response, with a positive predictive value of 84% and a negative predictive value of 82%. CONCLUSIONS: EVR can be applied to Chinese patients as an early stopping rule. A 24-week duration of pegylated IFN/ribavirin might be adequate for genotype 1 patients who rapidly responded to therapy.     

聚乙二醇干扰素仪-2α／2b联合利巴韦林复治慢性丙型肝炎患者的疗效观察

目的探讨聚乙二醇干扰素α（PEG-IFNα）联合利巴韦林治疗复发慢性丙型肝炎（CHC）患者的应答情况及影响因素。方法 30例经IFN-α或PEG-IFNα标准RGT治疗后复发的CHC患者,均用PEG-IFNα-2a（180μg）或PEG-IFNα-2b（1.5μg/kg）联合利巴韦林（900 mg/d）再治疗,基因1型治疗48周,非基因1型治疗24周,停药随访24周,分析病毒基因型、基线HCV RNA载量、初治药物种类对联合治疗疗效的影响。结果 30例复发患者经联合再治疗后,24例（80%）获得持续病毒学应答（SVR）。18例低病毒载量（HCV RNA≤105拷贝/ml）患者中,17例（94.4%）获得SVR,与高病毒载量组（58.3%）差异有统计学意义（P=0.026）。基因1型组18例,其中14例（77.8%）获得SVR,与非基因1型组（83.3%）差异无统计学意义（P=1.000）。初治应用PEG-IFNα联合利巴韦林抗病毒的患者17例,其中13例（76.5%）经再治疗后获得SVR,与初治应用IFN-α抗病毒组（84.6%）无明显差异（P=0.672）。结论 PEG-IFNα联合利巴韦林治疗复发CHC患者的疗效较好。基线病毒载量高,再治疗效果差;病毒基因型及初治所采用的IFN类型与再治疗的疗效无显著相关性。     

Prediction of sustained response to low‐dose pegylated interferon alpha‐2b plus ribavirin in patients with genotype 1b and high hepatitis C virus level using viral reduction within 2 weeks after therapy initiation

Aim: Continuation of pegylated interferon (PEG‐IFN) plus ribavirin at the recommended dose is difficult in elderly patients and/or patients with cytopenia or complications. Whether the therapeutic efficacy of low‐dose PEG‐IFN plus ribavirin therapy could be predicted based on virological response within 2 weeks of therapy initiation was evaluated. Methods: A total of 106 patients with a high viral load of genotype‐1b hepatitis C virus (HCV) underwent low‐dose PEG‐IFN plus ribavirin therapy. PEG‐IFN alpha 2b (0.75 µg/kg per week) and ribavirin (600–800 mg/day) were administered for 48 weeks. Results: Sustained virological response (SVR) was achieved in 37%, and treatment was discontinued in 9%. On univariate analysis of SVR‐contributing factors, significant differences were noted in the white blood cell count, platelet count, fibrosis markers, and viral reduction within 2 weeks from therapy initiation. On multivariate analysis, the platelet count and the reduction in the HCV core antigen level at week 2 were independent factors. The positive predictive value (PPV) and the negative predictive value (NPV) for SVR based on a 1‐log or greater HCV‐RNA level reduction at week 2 were 65% and 90%, respectively, and those based on HCV core antigen level at week 2 were 64% and 97%, respectively. PPV and NPV based on a 2‐log or greater reduction of the RNA level were 86% and 67%, respectively, and those based on the core antigen level were 93% and 69%, respectively. Conclusion: Evaluation of viral reduction at week 2 after therapy initiation is useful for predicting SVR to low‐dose PEG‐IFN plus ribavirin therapy.     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎患者疗效及其影响因素分析

目的：观察聚乙二醇干扰素（PEG IFNα-2a）联合利巴韦林（RBV）治疗慢性丙型肝炎（CHC）患者的疗效及其影响因素。方法对331例慢性丙型肝炎患者予 PEG IFNα-2a（180μg/w 或135μg/w）联合利巴韦林（RBV）900~1200 mg/d 抗病毒治疗,疗程48～72 w,随访24 w;治疗前检测丙型肝炎病毒基因型,采用 PCR 法检测丙型肝炎病毒（HCV）RNA 水平及肝功能,以病毒学应答和生化学应答作为疗效的主要评价指标。结果在331例CHC 患者中,获得快速病毒学应答率（RVR）、早期病毒学应答率（EVR）和持续病毒学应答率（SVR）分别为65%（215/331）、94.9%（314/331）和84.9%（281/331）;对176例行基因分型,结果108例基因1型与68例非1型感染者SVR 分别为88.0%和79.4%,两组比较无明显差异;75例血清 HCV RNA 水平小于4×105 IU/ml 的患者 SVR 为93.3%,高于256例 HCV RNA 水平大于4×105 IU/ml 患者的82.4%（P〈0.05）;215例获得 RVR 的 CHC 患者的SVR 明显高于116例未获得 RVR 患者（92.6%对70.7%,x2=28.099,P=0.000）,314例获得 EVR 患者的 SVR 也明显高于17例未获得 EVR 组（88.5%对17.6%,x2=63.194,P=0.000）;50例未获得 SVR 的 CHC 患者年龄和感染丙型肝炎病毒的时间分别为（46±15）岁和（14.8±8.0）年,显著大或长于281例获得 SVR 患者[（38±13）岁和（11.5±7.7）年,P 均〈0.05]。结论聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效较好,预测临床疗效的关键因素是患者年龄、感染丙型肝炎的病程、治疗前 HCV RNA 水平及在治疗过程中能否及时获得 RVR 和 EVR。     

Immediate virological response predicts the success of shortterm peg-interferon monotherapy for chronic hepatitis C

AIM:To investigate the efficacy of short-term peginterferon(PEG-IFN)monotherapy for chronic hepatitis C patients who achieved an immediate virological response.METHODS:Defining an“immediate virological response(IVR)“as the loss of serum hepatitis C virus(HCV) RNA 7 d after the first administration of PEG-IFNα,we conducted a 12-wk course of PEG-IFNα2a monotherapy without the addition of ribavirin for 38 patients who had low pretreatment HCV RNA load and exhibited IVR.The patients included 21 men and 17 women...     

Efficacy of a short‐term ribavirin plus interferon alpha combination therapy followed by interferon alpha alone in previously untreated patients with chronic hepatitis C: a randomized multicenter trial

Abstract: Background: Combination therapy with interferon alpha (IFNα) plus ribavirin has been shown to improve the sustained response rate in patients with chronic hepatitis C but there is little information regarding the lengths of time for this therapeutic regimen. In this study we therefore tried to evaluate whether the analysis of different virological parameters could provide new clues with respect to the early determination of the efficacy of this form of combination therapy. Furthermore, we also examined whether short‐term induction combination therapy followed by IFNα alone is more effective than monotherapy in mounting an initial as well as a sustained virological response. Methods: 185 patients with histologically proven chronic hepatitis C (mean age 42 years (range 19–65 years); 110 males, 75 females) were enrolled in the study. The patients were randomly assigned to receive, over the first 12 weeks, either interferon alpha 2a 6 million units (MU) three times weekly plus ribavirin 14 mg/kg per day (n=93) or the same dose of IFNα alone (n=92). Patients with a virological response (serum HCV RNA undetectable) after 12 weeks were subsequently treated with 3 MU IFNα alone thrice weekly for a further 40 weeks. Otherwise, treatment was discontinued. After the end of treatment, patients were followed up for 24 weeks. Results: Patient characteristics at baseline were not significantly different in the two treatment groups. An initial virological response at week 12 was seen in 61 (66%) patients receiving IFNα plus ribavirin and in 44 (48%) being treated with IFNα alone (p=0.015) and this improvement in the response rate was mainly restricted to HCV genotype 1‐infected patients (58% vs. 38%). In contrast, end‐of‐treatment (week 52) and sustained virological response rates were similar in both groups (37% vs. 29% and 26% vs. 17% [p=0.1], respectively). Interestingly, patients with HCV genotype 3, however, clearly benefited from short‐term combination therapy. Thus, sustained virological response rates in these patients significantly increased from 25% (IFNα monotherapy) to 59% (combination therapy) (p=0.05). Conclusions: Short‐term combined therapy for 12 weeks is more effective than the monotherapy with respect to the induction of an initial virological response but this effect applies only to genotype 1‐infected patients. However, there is no significant difference between both therapeutic schedules with regard to the induction of sustained response. Although HCV genotype 3‐infected patients seem to benefit from this short‐term combined therapy, prolonged combined therapy may be necessary in HCV genotype 1‐infected patients.     

Pioglitazone improves virological response to peginterferon α‐2b/ribavirin combination therapy in hepatitis C genotype 4 patients with insulin resistance

Background & aim: Insulin resistance (IR) affects sustained virological response (SVR). The use of insulin‐sensitizing agents has been proposed to improve therapy outcome. The safety and efficacy of pioglitazone on insulin sensitivity and SVR in treatment‐naïve patients with chronic hepatitis C (CHC) genotype 4 with IR receiving standard antiviral therapy were evaluated in a randomized‐controlled study. Methods: Ninety‐seven previously untreated patients with CHC and IR [homeostasis model assessment (HOMA>2)] were randomly assigned into two arms; (arm A; n=48) were given pioglitazone 30 mg/day combined with peginterferon (Peg‐IFN)‐α‐2b/ribavirin (RBV) for 48 weeks, and (arm B; n=49) were given standard of care (Peg‐IFN‐α‐2b/RBV for 48 weeks); HOMA index and hepatitis C virus RNA (HCV RNA) levels were measured at baseline, during therapy and follow‐up. Treatment was stopped in patients without an early virological response or those who were HCV RNA positive at 24 weeks. Results: Baseline data of both groups were comparable, with no significant statistical differences. The percentages of rapid virological response (RVR) and SVR were significantly higher in patients given triple therapy compared with standard of care (27.08 vs. 6.1%; P=0.006 and 60.4 vs. 38.7%; P=0.04 respectively); patients in arm A showed a greater decrease in the HOMA index than those in arm B (?1.8 ± 0.3, ?2.1 ± 0.3 vs. ?1.1 ± 0.6, ?1.3 ± 0.7) at week 24 and at the end of follow‐up (P=0.001 at both time points). The triple therapy was well tolerated. Conclusions: A combination of pioglitazone, Peg‐IFN‐α‐2b and ribavirin increased RVR, SVR and decreased IR, compared with patients given Peg‐IFN plus ribavirin without an increase in adverse events.