Efficacy of low dose peginterferon alpha-2b with ribavirin on chronic hepatitis C

INTRODUCTION The hepatitis C virus is a major cause of liver diseases affecting 170 million people worldwide[1]. In India, the estimated prevalence of hepatitis C virus infection is 1.8%. Genotypes 2 and 3 are predominant in Indian population[2]. Therapy …     

Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin

AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetopro...     

Impact of ribavirin dose on retreatment of chronic hepatitis C patients

AIM: To study the efficacy and factors associated with a sustained virological response (SVR) in chronic hepatitis C (CHC) relapsing patients.METHODS: Out of 1228 CHC patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV), 165 (13%) had a relapse. Among these, 62 patients were retreated with PEG-IFN-α2a or -α2b and RBV. Clinical, biological, virological and histological data were collected. Initial doses and treatment modifications were recorded. The efficacy of retreatment and predictive factors for SVR were analyzed.RESULTS: An SVR was achieved in 42% of patients. SVR was higher in young (< 50 years) (61%) than old patients (27%) (P = 0.007), and in genotype 2 or 3 (57%) than in genotype 1 or 4 (28%) patients (P = 0.023). Prolonging therapy for at least 24 wk more than the previous course was associated with higher SVR rates (53% vs 28%, P = 0.04). Also, a better SVR rate was observed with RBV dose/body weight > 15.2 mg/kg per day (70% vs 35%, P = 0.04). In logistic regression, predictors of a response were age (P = 0.018), genotype (P = 0.048) and initial RBV dose/body weight (P = 0.022). None of the patients without a complete early virological response achieved an SVR (negative predictive value = 100%).CONCLUSION: Retreatment with PEG-IFN/RBV is eff-ective in genotype 2 or 3 relapsers, especially in young patients. A high dose of RBV seems to be important for the retreatment response.     

聚乙二醇干扰素α-2a联合利巴韦林治疗ALT正常的慢性丙型肝炎疗效观察

目的评价聚乙二醇(PEG)干扰素联合利巴韦林治疗ALT正常的慢性丙型肝炎的临床疗效。方法使用聚乙二醇干扰素α-2a联合利巴韦林治疗20例ALT正常和25例ALT升高的慢性丙型肝炎患者。分别于治疗12周、48周及治疗结束后24周评价疗效,并观察药物副反应。结果ALT正常组所有患者均完成治疗,在治疗12周时的早期应答率为45%(9/20),治疗结束时的应答率为55%(11/20),在治疗结束后随访24周,持续应答率为45%(9/20)。2例患者在随访24周内出现ALT升高,血清HCVRNA阳转,复发率为18.2%(2/11),所有疗效指标与ALT升高组对比均无显著差异。结论PEG干扰素联合利巴韦林治疗ALT正常的慢性丙型肝炎同样具有较好的临床疗效,且副反应较轻。     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察

目的评价聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的临床疗效。方法使用聚乙二醇干扰素α-2a(派罗欣)联合利巴韦林(800~1200mg/d)治疗58例慢性丙型肝炎患者,疗程48周,分别于治疗12周、24周和48周及治疗结束后24周评价疗效,并观察药物副作用。结果基因1型和非基因1型患者早期应答率分别为57.1%和76.7%(P>0.05),持续应答率分别为53.6%和80.0%(P<0.05);HCV RNA高水平组和低水平组之间持续应答率分别为56.3%和80.8%,具有显著性差异(P<0.05)。结论在慢性丙型肝炎患者的治疗中,基因1型患者疗效低于非基因1型,HCV RNA低水平组的疗效优于高水平组。     

Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1

AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin (pegIFN/RBV), in treatment-naive hepatitis C virus (HCV) genotype (GT) 1-infected patients.METHODS: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned (2:1) to daclatasvir vs telaprevir, stratified by IL28B rs12979860 host genotype (CC vs non-CC), cirrhosis status (compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype (GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus pegIFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus pegIFN/RBV; those without an extended rapid virologic response (eRVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of pegIFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus pegIFN/RBV followed by 12 (with eRVR) or 36 (no eRVR) wk of pegIFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12 (SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia (hemoglobin < 10 g/dL) and rash-related events, through week 12, were lower with daclatasvir + pegIFN/RBV than with telaprevir + pegIFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/mL, to investigate any link between NS5A polymorphisms associated with daclatasvir resistance and virologic outcome.RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups (6.0% and 8.2% in the GT1b and GT1a groups, respectively) than in the telaprevir groups (2.2% and 3.0%). Among GT1b-infected patients, daclatasvir plus pegIFN/RBV was noninferior to telaprevir plus pegIFN/RBV for SVR12 [85% (228/268) vs 81% (109/134); difference, 4.3% (95%CI: -3.3% to 11.9%)]. Anemia (hemoglobin < 10 g/dL) was significantly less frequent with daclatasvir than with telaprevir [difference, -29.1% (95%CI: -38.8% to -19.4%)]. Rash-related events were also less common with daclatasvir than with telaprevir, but the difference was not statistically significant. In GT1a-infected patients, SVR12 was 64.9% with daclatasvir and 69.7% with telaprevir. Among both daclatasvir and telaprevir treatment groups, across GT1b- or GT1a-infected patients, lower response rates were observed in patients with IL28B non-CC and cirrhosis - factors known to affect response to pegIFN/RBV. Consistent with these observations, a multivariate logistic regression analysis in GT1b-infected patients demonstrated that SVR12 was associated with IL28B host genotype (CC vs non-CC, P = 0.011) and cirrhosis status (absent vs present, P = 0.031). NS5A polymorphisms associated with daclatasvir resistance (at L28, R30, L31, or Y93) were observed in 17.3% of GT1b-infected patients at baseline; such variants did not appear to be absolute predictors of failure since 72.1% of these patients achieved SVR12 compared with 86.9% without these polymorphisms. Among GT1b-infected patients, treatment was completed by 85.4% (229/268) in the daclatasvir group, and by 85.1% (114/134) in the telaprevir group, and among GT1a-infected patients, by 67.2% (90/134) and 69.7% (46/66), respectively. Discontinuations (of all 3 agents) due to an AE were more frequent with telaprevir than with daclatasvir, whereas discontinuations due to lack of efficacy were more frequent with daclatasvir, due, in part, to differences in futility criteria.CONCLUSION: Daclatasvir plus pegIFN/RBV demonstrated noninferiority to telaprevir plus pegIFN/RBV for SVR12 and was well-tolerated in treatment-naive GT1b-infected patients, supporting the use of daclatasvir with other direct-acting antivirals.     

Pegylated Interferon and Ribavirin in the Retreatment of Chronic Hepatitis C in Korea

Background/Aims

Pegylated interferon (peginterferon) and ribavirin is the current standard therapy for chronic hepatitis C. The aims of this study were to evaluate the efficacy of peginterferon and ribavirin and to identify predictors of a sustained virological response (SVR) to the retreatment of chronic hepatitis C in Korea.

Methods

The clinical records of 91 patients with chronic hepatitis C who were retreated with peginterferon and ribavirin were retrospectively analyzed. None of the patients had previously attained a SVR, and the patients were categorized according to their previous responses (nonresponder, relapser, or inadequate treatment) to conventional interferon/ribavirin.

Results

The overall SVR rate was 54.9%. Independent predictors of a SVR were genotypes 2 and 3, relapse, an adherence to peginterferon of over 80%, and an early virological response (EVR). For genotype 1 patients, an adherence to peginterferon of over 80% was an independent predictor of a SVR.

Conclusions

Peginterferon and ribavirin therapy is effective for the retreatment of Korean chronic hepatitis C patients who have failed interferon/ribavirin, especially in patients with genotypes 2 and 3, relapse, an adherence to peginterferon over 80%, and an EVR. For genotype 1 patients, retreatment was effective in patients with an adherence to peginterferon over 80%.     

Boceprevir plus peginterferon/ribavirin for treatment of chronic hepatitis C in Russia

AIM: to evaluate addition of boceprevir to peginterferon/ribavirin(PR) in Russian patients with chronic hepatitis C virus(HCV).METHODS: treatment-naive(t N) and treatmentexperienced(t E) patients(who had failed prior treatment with PR for ≥ 12 wk) with chronic HCV genotype 1 infection were enrolled in this placebocontrolled, double-blind study. All patients initially received PR for 4 wk. Patients randomized to control treatment then received PR for an additional 44 wk. t N patients randomized to triple therapy received boceprevir(800 mg three times daily) plus PR for 24 wk and then further therapy according to treatment week 8(t W8) HCV RNA levels. t E patients received boceprevir plus PR for 32 wk and then further therapy according to t W8 HCV RNA levels. treatment was discontinued for t N patients with detectable HCV RNA at t W24 and t E patients with detectable HCV RNA at t W12 because of futility. the primary efficacy end point was sustained virologic response(SVR) defined as undetectable HCV RNA 24 wk after completing all study therapy.RESULTS: SVR was 74.8% in the boceprevir plus PR arm compared with 46.2% in the control arm, with a stratification-adjusted treatment difference of 29.2%(95%CI: 16.4-41.5; P 0.0001). Rates of SVR were higher in the boceprevir arm in both t N and t E patient groups(t N 78.4% vs 56.3%; t E 69.4% vs 30.0%). Within t E patients, the rates of SVR were higher with boceprevir plus PR compared with PR, regardless of treatment failure type(null responder, partial responder, and relapser). Most patients receiving boceprevir plus PR in both t N(86%) and t E(71%) populations were eligible for reduced treatment duration. Anemia was increased in patients receiving boceprevir plus PR vs PR alone(47.2% vs 24.4%); there was a corresponding increase in ribavirin dose reduction and erythropoietin use. Among patients receiving boceprevir plus PR, SVR rates were similar in patients with anemia( 10 g/d L) and those without anemia(71.2% vs 77.4%).CONCLUSION: Regulatory approval has been obtained for boceprevir plus PR in Russian patients with HCV genotype 1 infection based on the results of this study.     

慢性丙型肝炎干扰素治疗后复发患者干扰素联合利巴韦林再治疗

目的 探讨干扰素（IFN）治疗后复发的慢性丙型肝炎（CHC）患者对IFN联合利巴韦林再治疗的应答情况及影响因素。方法 100例IFN治疗后复发的CHC患者中，50例使用聚乙二醇干扰素α-2a（PEG—IFNα-2a），50例使用重组人干扰素α-1b（CIFNα—1b），均联合利巴韦林再治疗，联合治疗48周，停药随访24周，分析HCVRNA载量、病毒基因型、药物种类对联合治疗疗效的影响。结果 100例复发患者联合再治疗后，36．00％取得持续病毒学应答（SVR），其中PEG-IFNα-2a组48．00％取得SVR，显著高于CIFNα—1b组（24．00％，P〈0．05）。56例低病毒载量（HCV-RNA〈1×10^5拷贝／mL）患者中，PEG—IFNα-2a组28例，其中57．14％取得SVR，显著高于CIFNα—1b组（25．00％，P〈0．05）。HCV非基因1（2a或2b）型组29例，其中55．17％取得SVR，显著高于基因1型组（28．20％，P〈0．05）；在CIFNα—1b治疗组，病毒非基因1型17例患者，其中47．06％取得SVR，明显高于基因1型患者（12，12％，P〈0．01）；在基因1型组，PEG—IFNα-2a组38例，其中42．11％取得SVR，显著高于CIFNα—1b组（12．12％，P〈0.01）。结论 IFN治疗后复发的CHC患者IFN联合利巴韦林再治疗存在部分患者无应答；对于HCV病毒载量低、基因1型的复发患者，聚乙二醇干扰素联合利巴韦林再治疗疗效明显优于普通干扰素的联合治疗。     

Pegylated interferon plus ribavirin for genotype Ib chronic hepatitis C in Japan

AIM：To evaluate the efficacy of pegylated interferon α-2b（peg-IFNα-2b） plus ribavirin（RBV） therapy in Japanese patients with chronic hepatitis C（CHC） genotype Ib and a high viral load.METHODS：One hundred and twenty CHC patients（58.3% male） who received peg-IFNα-2b plus RBV therapy for 48 wk were enrolled.Sustained virological response（SVR） and clinical parameters were evaluated.RESULTS：One hundred（83.3%） of 120 patients completed 48 wk of treatment.53 patients（44.3%） achieved SVR.Early virological response（EVR） and end of treatment response（ETR） rates were 50% and 73.3%,respectively.The clinical parameters（SVR vs non-SVR） associated with SVR,ALT（108.4 IU/L vs 74.5 IU/L,P = 0.063）,EVR（76.4% vs 16.4%,P 〈 0.0001）,adherence to peg-IFN（≥ 80% of planned dose） at week 12（48.1% vs 13.6%,P = 0.00036）,adherence to peg-IFN at week 48（54.7% vs 16.2%,P 〈 0.0001） and adherence to RBV at week 48（56.1% vs 32.1%,P = 0.0102） were determined using univariate analysis,and EVR and adherence to peg-IFN at week 48 were determined using multivariate analysis.In the older patient group（〉 56 years）,SVR in females was significantly lower than that in males（17% vs 50%,P = 0.0262）.EVR and adherence to Peg-IFN were demonstrated to be the main factors associated with SVR.CONCLUSION：Peg-IFNα-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients with CHC and resulted in a SVR rate of 44.3%.Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFNα-2b is important in improving the SVR rate.     

Direct-acting antiviral-based triple therapy on alpha-fetoprotein level in chronic hepatitis C patients

AIM: To investigate the impact of telaprevir-based triple therapy on the serum alpha-fetoprotein (AFP) level of chronic hepatitis C patients.METHODS: A total of 210 patients with chronic hepatitis C genotype 1 of high viral load (baseline serum hepatitis C virus RNA > 5.0 log₁₀ IU/mL) were divided into two groups by type of treatment: triple therapy with telaprevir, pegylated-interferon-α (PEG-IFNα), and ribavirin (RBV) for 24 wk (n = 88), or dual therapy with PEG-IFNα and RBV for 48 wk (n = 122). The relationship between virological response and the change in the serum AFP level from baseline to 24 wk after the end of treatment was examined.RESULTS: No significant difference in mean baseline AFP level was found between the triple and dual therapy groups (8.8 ng/mL vs 7.8 ng/mL). Triple therapy produced significant declines in the AFP level in sustained virological response (SVR) and non-SVR patients (7.8 ng/mL at baseline to 3.5 ng/mL at 24 wk after the end of treatment, P < 0.001 and 14.3 ng/mL to 9.5 ng/mL, P = 0.004, respectively). In contrast, dual therapy resulted in a significant decline in AFP level only in SVR patients (4.7 ng/mL to 2.8 ng/mL, P < 0.001), but not in non-SVR patients (10.2 ng/mL to 10.1 ng/mL). Among patients with a high-baseline AFP level (≥ 10 ng/mL), the decline in the AFP level was significantly higher in the triple therapy than in the dual therapy group (15.9 ng/mL vs 1.6 ng/mL, P = 0.037).CONCLUSION: Regardless of virological response, telaprevir-based triple therapy reduced the serum AFP level.     

Pioglitazone in chronic hepatitis C not responding to pegylated interferon-alpha and ribavirin

BACKGROUND/AIMS: Insulin resistance reduces the response to interferon alfa-based therapy of chronic hepatitis C patients. It has been speculated that improvement of insulin sensitivity might increase the chances of responding to treatment of such individuals. METHODS: We started a multicenter clinical trial of retreatment of chronic hepatitis C patients, who had failed to respond to the pegylated interferon alfa/ribavirin combination, with a triple therapy consisting in these same antivirals plus an insulin-sensitizer (pioglitazone) (The INSPIRED-HCV study). RESULTS: None of the first five patients fulfilling the inclusion criteria and included in the trial achieved a satisfactory virological response after 12 weeks of retreatment, despite the fact that in at least three of them the insulin resistance score improved. As a result, the study was terminated. CONCLUSIONS: Different schedules are warranted to improve insulin sensitivity prior to attempting retreatment of chronic hepatitis C patients with insulin resistance.     

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。     

Peginterferon and ribavirin in HCV: Improvement of sustained viral response

Peginterferon alfa in combination with ribavirin is and will remain for the next years the current standard for treatment of chronic hepatitis C. The new antivirals currently investigated in phase II of III trials may augment the overall response rates but require peginterferon/ribavirin as backbone. The cure rate of peginterferon/ribavirin treatment can be improved by better education of treating physicians to identify and treat conditions which negatively influence the final outcome of therapy. Specific focus is the prevention and/or early treatment of common side effects of therapy including anaemia, cytopenia and depression. Measuring the viral response at various time points during treatment allows individualization of treatment duration. Based on these recent findings the treatment algorhytms for chronic hepatitis C will be reformulated (Figure 2 and Figure 3). The soon to be released German consensus statement for treatment of chronic hepatitis C will incorporate these recommendations.

1. Peginterferon/ribavirin is and will remain for the foreseeable future the standard of care for the treatment of chronic hepatitis C.

2. Sustained viral elimination (‘cure’) can be reached in about 50% of patients with genotypes 1 and 4, and in 70–80% of patients with genotypes 2 and 3. The major limitations for successful treatment in virologic responders are the well-known side effects of therapy. They may lead to decreased drug exposure or even early discontinuation of therapy.

3. Better education of treaters will improve side effect management and thus augment response rates.

4. Adaptation of treatment duration according to the rapidity of viral response is an important step for further improvement of outcome.

5. The impact of the new antiviral agents currently under investigation is unknown, but there is a great expectation that far more patients can be cured in future.

Effect of interferon and ribavirin combined with amantadine in interferon and ribavirin non-responder patients with chronic hepatitis C （genotype 1）

AIM: To evaluate the efficacy of amantadine plus interferon-alpha and ribavirin in non-responder patients with chronic hepatitis C. METHODS: Twenty-six non-responder patients received the regimen of IFN-α-2a at a dose of 6 million units three times a week, 1 000-1 200 mg of ribavirin daily, and 200 mg of amantadine daily in divided doses over 48 wk. After the end of treatment, at the 72nd wk, a sustained viral response rate was determined. RESULTS: An early (after 12 wk of therapy) response was seen in 34.6% (9/26) of patients. Response rate at the 24th wk was 42.3% (11/26). End of treatment response (ETR) was 53.8% (14/26). Sustained viral response (SVR) was 42.3% (11/26). There was a statistically significant difference between 0 and 12 wk (P= 0.04), 0 and 24 wk (P= 0.01), 0 and 48 wk (P= 0.00), and 0 and 72 wk (P= 0.001). No patient had severe adverse effects during the treatment. CONCLUSION: Combination regimen of interferon-α, ribavirin and amantadine can enhance sustained viral response on IFN-α and ribavirin non-responder patients with HCV. Triple therapy with amantadine should be evaluated in further studies.     

Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy. RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%) despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic changes in the optic fundi. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P = 0.004, OR = 245.918, 95% CI = 5.6-10786.2). CONCLUSION: Retinopathy associated with combination therapy of interferon alpha-2b and ribavirin tends to develop in patients with hypertension.     

Efficacy and tolerability of peginterferon alpha plus ribavirin in the routine daily treatment of chronic hepatitis C patients in Korea: a multi-center, retrospective observational study

Background/Aims

We aimed to evaluate the efficacy and safety of peginterferon plus ribavirin for chronic hepatitis C (CHC) patients under real life setting in Korea.

Methods

We retrospectively analyzed the medical records of 758 CHC patients treated with peginterferon plus ribavirin between 2000 and 2008 from 14 university hospitals in the Gyeonggi-Incheon area in Korea.

Results

Hepatitis C virus (HCV) genotype 1 was detected in 61.2% of patients, while genotype 2 was detected in 35.5%. Baseline HCV RNA level was ≥6×10⁵ IU/mL in 51.6% of patients. The sustained virological response (SVR) rate was 59.6% regardless of genotype; 53.6% in genotype 1 and 71.4% in genotype 2/3. On multivariate analysis, male gender (p=0.011), early virological response (p<0.001), genotype 2/3 (p<0.001), HCV RNA <6×10⁵ IU/mL (p=0.005) and adherence to the drug >80% of the planned dose (p<0.001) were associated with SVR. The rate of premature discontinuation was 35.7%. The main reason for withdrawal was intolerance to the drug due to common adverse events or cytopenia (48.2%).

Conclusions

Our data suggest that the efficacy of peginterferon and ribavirin therapy in Koreans is better in Koreans than in Caucasians for the treatment of CHC, corroborating previous studies that have shown the superior therapeutic efficacy of this regimen in Asians.     

Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy.METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy.RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%)despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension,or pretreatment arteriosclerotic changes in the optic fundj. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P=0.004,OR=245.918, 95% CI=5.6-10786.2).CONCLUSION: Retinopathy associated with combination therapy of interferon α-2b and ribavirin tends to develop in patients with hypertension.     

Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C

Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.     

Co-infection of SENV-D among chronic hepatitis C patients treated with combination therapy with high-dose interferon-alfa and ribavirin

AIM: The clinical significance of co-infection of SENV-D among patients with chronic hepatitis C (CMC) and response of both viruses to combination therapy with high-dose interferon-alfa (IFN) plus ribavirin remain uncertain and are being investigated. METHODS: Total 164 (97 males and 67 females, the mean age 48.1±11.4 years, range: 20-73 years, 128 histologically proved) naive CMC patients were enrolled in this study. SENV-D DNA was tested by PCR method. Detection of serum HCV RNA was performed using a standardized automated qualitative RT-PCR assay (COBAS AMPLICOR HCV Test, version 2.0). HCV genotypes la, 1b, 2a, 2b, and 3a were determined by using genotype-specific primers. Pretreatment HCV RNA levels were determined by using the branched DNA assay (Quantiplex HCV RNA 3.0). There are 156 patients receiving combination therapy with IFN 6 MU plus ribavirin for 24 wk and the response to therapy is determined. RESULTS: Sixty-one (37.2%) patients were positive for SENV-D DNA and had higher mean age than those who were negative (50.7±10.6 years vs46.6±11.6 years, P= 0.026). The rate of sustained viral response (SVR) for HCV and SENV-D were 67.3% (105/156) and 56.3% (27/48), respectively. By univariate analysis, the higher rate of SVR was significantly related to HCV genotype non-1b (P<0.001), younger ages (P = 0.014), lower pretreatment levels of HCV RNA (P = 0.019) and higher histological activity index (HAI) score for intralobular regeneration and focal necrosis (P= 0.037). By multivariate analyses, HCV genotype non-lb, younger age and lower pretreatment HCV RNA levels were significantly associated with HCV SVR (odds ratio (OR)/95% confidence interval (CI): 12.098/0.02-0.19, 0.936/0.890-0.998, and 3.131/1.080-9.077, respectively). The SVR of SENV-D was higher among patients clearing SENV-D than those who had viremia at the end of therapy (P= 0.04). CONCLUSION: Coexistent SENV-D infection, apparently associated with higher ages, is found in more than one-third Taiwanese CHC patients. Both HCV and SENV-D are highly susceptible to combination therapy with high-dose IFN and ribavirin and SENV-D co-infection does not affect the HCV response. HCV genotype, pretreatment HCV RNA levels and age are predictive factors for HCV SVR.