Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: Incidence, associated factors and prognosis

Abstract Background and Aims: Interferon (IFN) plus ribavirin therapy for chronic hepatitis C (CHC) virus infection has been associated with thyroid dysfunction. The goal of our current study was to elucidate predictive factors of: (i) thyroid dysfunction associated with combination therapy; and (ii) long‐term reversibility of thyroid dysfunction. Methods: In total, 461 patients with CHC and normal baseline thyroid functions were enrolled. All patients received IFN‐α‐2b, 3 or 5 million units thrice weekly, or pegylated (PEG)‐IFN‐α‐2b 80 or 100 µg weekly combined with ribavirin 1–1.2 g daily for 24–48 weeks. Assays for serum thyroid stimulating hormone (TSH) and free thyroxine were performed. Results: By the end of the treatment, thyroid dysfunction (TSH <0.1 or >5 mU/L) had developed in 58 patients (12.6%). Female gender was significantly associated with thyroid dysfunction (P < 0.001 odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.6–5.1). The incidence of thyroid dysfunction was similar for standard IFN and PEG‐IFN‐treated patients (49/391 vs 9/70; P = 1.00). Under a nested case‐control design, detailed laboratory assessment was carried out on frozen serum samples from patients and age‐ (± 5 years) and sex‐matched controls (n = 58). Multivariate analysis revealed significant association between higher positive rates of pretreatment TMA and patients who developed thyroid dysfunction (OR = 5.8, 95% CI = 1.2–27.9). Ten patients (～2%) remained thyroid dysfunctional at the end of follow up (median, 26.5 months). For these patients, no risk factor can predict the reversibility of thyroid function. Conclusions: Female gender and pretreatment TMA positivity are associated with thyroid dysfunction. Long‐term thyroid dysfunction may persist in a small group of patients (～2%).     

Short-term prolongation of pegylated interferon and ribavirin therapy for genotype 1b chronic hepatitis C patients with early viral response

Aim:  We tailored extended treatments using pegylated interferon (PEG IFN) and ribavirin (RBV) to viral responses after initiation of therapy and investigated the efficacy and safety of its therapy for chronic hepatitis C (CHC) patients.
Methods:  Eighty-two genotype 1b CHC patients were enrolled in the present study. All patients received PEG IFN-α-2b and weight-based RBV therapy. We defined a viral response in which serum HCV-RNA is undetectable at week 4 as rapid viral response (RVR), detectable at week 4 and undetectable by week 12 as early viral response (EVR), and detectable at week 12 and undetectable by week 24 as late viral response (LVR). We set the treatment duration depending on viral response; 48 weeks for RVR patients and 72 weeks for LVR. Furthermore, EVR patients received a short-term extension of treatment duration to 52–60 weeks. We prospectively investigated sustained viral response (SVR) rates of these groups.
Results:  Overall SVR rate for the total patient group was 57.3%. SVR rates of the RVR, EVR and LVR patients were 100%, 80.5% and 40.0%, respectively. Nine patients could not complete this treatment protocol. Baseline platelet count and mutation in the interferon sensitivity-determining region of NS5A were significant independent predictors of SVR, and amino acid substitution of the core region was a significant independent predictor of non-viral response by multivariate logistic regression analyses.
Conclusion:  The results indicate that short-treatment extension of PEG IFN plus RBV treatment protocols in EVR patients can improve overall SVR rates.     

Adequate timing of ribavirin reduction in patients with hemolysis during combination therapy of interferon and ribavirin for chronic hepatitis C

Background Hemolytic anemia is one of the major adverse events of the combination therapy of interferon and ribavirin. Because of ribavirin-related hemolytic anemia, dose reduction is a common event in this therapy. In this clinical retrospective cohort study we have examined the suitable timing of ribavirin reduction in patients with hemolysis during combination therapy.Methods Thirty-seven of 160 patients who had HCV-genotype 1b, had high virus load, and received 24-week combination therapy developed anemia with hemoglobin level <10g/dl or anemia-related signs during therapy. After that, these 37 patients were reduced one tablet of ribavirin (200mg) per day. After reduction of ribavirin, 27 of 37 patients could continue combination therapy for a total of 24 weeks (group A). However, 10 of 37 patients with reduction of ribavirin could not continue combination therapy because their <8.5g/dl hemoglobin values decreased to or anemia-related severe side effects occurred (group B). We assessed the final efficacy and safety after reduction of ribavirin in groups A and B.Results A sustained virological response (SVR) was 29.6% (8/27) in group A and 10% (1/10) in group B, respectively. A 34.4% (12/27) of SVR + biological response in group A was higher than 10% (1/10) in group B (P = 0.051), with slight significance. With respect to hemoglobin level at the time of ribavirin reduction, a rate of continuation of therapy in patients with 10g/dl hemoglobin was higher than that in patients with <10g/dl (P = 0.036).Conclusions Reduction of ribavirin at hemoglobin level 10g/dl is suitable in terms of efficacy and side effects.     

Thyroid disorders during interferon alpha therapy in 625 patients with chronic hepatitis C: a prospective cohort study

AIM: to report the prevalence, risk factors, management and long-term outcome of thyroid disorders caused by INFalpha in patients with chronic hepatitis C. PATIENTS AND METHODS: From January 1991 to December 2004, 625 patients with chronic hepatitis C underwent INFalpha therapy. TSH assay was normal and antithyroperoxidase antibodies (anti-TPO) was performed before onset antiviral treatment; then TSH was performed every 2 months in all patients during therapy, and every 3 months after treatment. RESULTS: 58 patients developed thyroid disorder (8.9%). Mean age was 50.6+/-13 years; sex ratio: 1 M/2 F; the anti-TPO antibodies were positive before onset antiviral treatment in 9 patients (13.8%). 26 patients developed hypothyroidism (44.8%), 9 patients developed hyperthyroidism (15.5%) and among them 3 cases of Grave's disease. Biphasic thyroiditis occurred in 21 patients (36.2%), anti-TPO increase during treatment in 2 patients (3.5%) without hypothyroidism. The dysthyroidism was more frequent in risk in female gender (p<0.05) and in the group with positive antiTPO antibodies before treatment (p<0.02). CONCLUSION: Female gender and positive antiTPO antibodies are the predictive factors of development of the thyroid dysfunction during INFalpha therapy.     

Weight loss during pegylated interferon and ribavirin treatment of chronic hepatitis C*

SUMMARY: Treatment of hepatitis C virus (HCV) infection with interferon (IFN)-alpha, as monotherapy or in combination with ribavirin, is associated with significant side-effects including weight loss. The aim of our study was to describe the evolution of body weight during combination antiviral treatment and to examine the possible determinants of weight loss. This was a retrospective analysis of 126 patients who received combination therapy of pegylated IFN-alpha-2b and ribavirin at our unit. Body weight was recorded at each outpatient attendance during treatment and follow-up, and was expressed as a percentage of baseline value. We observed a decline of body weight during treatment. Median (range) weight values at 4, 12, 24, and 48 weeks (expressed as percentage of baseline weight) were 97.7 (91.5-110.2), 95.4 (84.4-109.4), 93.7 (80.8-106.5), and 91.1 (80.1-103.6) respectively. There was no significant association of increased weight loss with age, gender, pretreatment weight, ethnicity, pretreatment histological stage, cumulative IFN dose (adjusted for body weight), HCV genotype or treatment outcome. Median body weight returned to baseline within 6 months of stopping treatment. Patients experience significant weight loss during combination therapy. Those experiencing greater weight losses during therapy did not benefit from improved antiviral response.     

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.     

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.     

Orally administered Kampo medicine,Juzen-taiho-to,ameliorates anemia during interferon plus ribavirin therapy in patients with chronic hepatitis C

Background Interferon plus ribavirin (IFN/Rib) therapy is currently standard treatment for chronic hepatitis C. Hemolytic anemia, however, is a serious side effect of this treatment, requiring reductions in or complete withdrawal of ribavirin.Methods We retrospectively investigated the effect of the Kampo medicine Juzen-taiho-to (TJ-48), which contains bone marrow-stimulating compounds, on anemia in 67 patients with chronic hepatitis C, who received IFN/Rib therapy.Results The reduction in hemoglobin levels was significantly ameliorated in TJ-48-treated patients (P < 0.05). Consequently, only 13% (4/32) of TJ-48-treated patients received altered doses of ribavirin, while the ribavirin dose had to be reduced or withdrawn in 43% (15/35) of patients in the absence of TJ-48 administration (P < 0.001).Conclusions These results indicate the possibility that oral administration of TJ-48 supports IFN/Rib therapy without necessitating ribavirin reduction or withdrawal.     

The role of thyroid autoantibodies in the development of thyroid dysfunction in Taiwanese chronic hepatitis C patients with interferon-alpha and ribavirin combination therapy

Summary. To investigate the role of thyroid autoantibodies in the development of thyroid dysfunction among chronic hepatitis C (CHC) patients receiving interferon‐alpha (IFN‐α) plus ribavirin (RBV) combination therapy, 95 Taiwanese naïve patients with baseline euthyroidism were enrolled. They were treated with IFN‐α2b, 6 million units thrice weekly, plus RBV 1000–1200 mg daily for 24 weeks. Thyroid function, anti‐thyroglobulin and antiperoxidase autoantibodies were tested at enrolment (M0), at the end‐of‐treatment (M6) and 6 months after end‐of‐treatment (M12). The percentages of thyroid autoantibodies were 8.4%, 11.6% and 9.5%, at M0, M6 and M12 respectively. Fourteen (14.7%) patients developed thyroid dysfunction at M6 or M12. Thyroid dysfunction occurred during treatment in five (62.5%) of the eight patients with baseline thyroid autoantibodies, which was significantly higher than nine (10.3%) of 87 patients without baseline thyroid autoantibodies (P = 0.0001). Among 14 patients who developed thyroid dysfunction, four (80.0%) of five patients with baseline thyroid autoantibodies recovered at M12, in contrast to two (25%) of eight without baseline thyroid autoantibodies recovered at M12 (P < 0.05). In conclusion, thyroid autoantibodies, either occurred before or during IFN‐α plus RBV combination therapy, carry a high prediction of subsequent thyroid dysfunction. There also exists difference in the clinical manifestations of thyroid dysfunction in CHC patients treated with combination therapy.     

Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1

Background and Aims: Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1. Methods: Seventy patients with either genotype 6 or genotype 1 were recruited. Both groups received 800–1200 mg of ribavirin daily plus either 180 mg of pegylated α‐interferon‐2a or 1.5 mg/kg pegylated α‐interferon‐2b weekly for 48 weeks. Their responses to treatments were compared. Results: The early virological response to combination therapy of patients with genotype 6 was significantly better than that of genotype 1 (88.6% vs 74.3%, P = 0.03). Significant difference was also identified in the end of treatment response of the two genotypes (60% vs 81.4% for genotype 1 and 6, respectively; P = 0.005). The sustained virological response (SVR) to treatment in patients with genotype 6 was also significantly superior to that of patients with genotype 1 (75.7% vs 57.1%, P = 0.02). Multiple logistic regression analysis demonstrated that age of 55 years or less, genotypes of hepatitis C virus, liver biopsy staging and baseline hepatitis C virus RNA of 200 000 IU/mL or less were independent predictors for better SVR in this cohort. Conclusion: Patients with chronic hepatitis C genotype 6 respond better to pegylated interferon and ribavirin combination treatment than patients with genotype 1.     

A multicenter survey of re‐treatment with pegylated interferon plus ribavirin combination therapy for patients with chronic hepatitis C in Japan

Aim: This study aimed to clarify the factors associated the efficacy of re‐treatment with pegylated interferon (PEG IFN) plus ribavirin combination therapy for patients with chronic hepatitis C who had failed to respond to previous treatment. Methods: One hundred and forty‐three patients who had previously shown relapse (n = 79), non‐response (n = 34) or intolerance (n = 30) to PEG IFN plus ribavirin were re‐treated with PEG IFN plus ribavirin. Results: Twenty‐five patients with intolerance to previous treatment completed re‐treatment and the sustained virological response (SVR) rates were 55% and 80% for hepatitis C virus (HCV) genotype 1 and 2, respectively. On re‐treatment of the 113 patients who completed the previous treatment, the SVR rates were 48% and 63% for genotype 1 and 2, respectively. Relapse after previous treatment and a low baseline HCV RNA level on re‐treatment were associated with SVR in genotype 1 (P < 0.001). Patients with the interleukin‐28B major genotype responded significantly better and earlier to re‐treatment, but the difference in the SVR rate did not reach a significant level between the major and minor genotypes (P = 0.09). Extended treatment of 72 weeks raised the SVR rate among the patients who attained complete early virological response but not rapid virological response with re‐treatment (72 weeks, 73%, 16/22, vs 48 weeks, 38%, 5/13, P < 0.05). Conclusion: Relapse after previous treatment and a low baseline HCV RNA level have predictive values for a favorable response of PEG IFN plus ribavirin re‐treatment for HCV genotype 1 patients. Re‐treatment for 72 weeks may lead to clinical improvement for genotype 1 patients with complete early virological response and without rapid virological response on re‐treatment.     

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。     

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.     

Decline in pulmonary function during chronic hepatitis C virus therapy with modified interferon alfa and ribavirin

Rare interstitial lung disease cases have been reported with albinterferon alfa‐2b (albIFN) and pegylated interferon alfa‐2a (Peg‐IFNα‐2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg‐IFNα‐2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety‐one patients were randomly assigned 4:4:4:3 to one of four, open‐label, 24‐week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 μg q4wk or Peg‐IFNα‐2a 180 μg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X‐rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg‐IFNα‐2a and albIFN 1500 μg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg‐IFNα‐2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long‐term pulmonary function impairment warrant further research.     

Impact of early elevation of serum bilirubin during treatment with pegylated interferon and ribavirin in patients with chronic hepatitis C

Aim: Hemolytic anemia is a well‐known adverse effect of interferon and ribavirin combination treatment. Herein, we analyzed the impact of early elevation of serum bilirubin level as a marker for predicting severe anemia during treatment. Methods: We studied 245 chronic hepatitis C patients who received pegylated interferon and ribavirin combination treatment, and divided them using two different threshold levels: (i) elevation of total bilirubin of 0.5 mg/dL or more within 1 week of starting treatment; and (ii) drop of hemoglobin (Hb) by 3 g/dL or more within 4 weeks of starting treatment. We compared the dynamics in each group and then investigated independent factors for predicting a severe Hb drop (≥3 g/dL) at 4 weeks after beginning treatment and dose reduction of ribavirin. Results: Total bilirubin levels at 1 week were significantly higher in patients with a Hb drop of 3 g/dL or more as compared to those with a drop of less than 3 g/dL (P < 0.0001). Hb levels at 4 weeks were significantly lower in the group of 0.5 mg/dL or more increase of total bilirubin levels than in the group with a less than 0.5 mg/dL increase (P < 0.0001). Therefore, elevation of total bilirubin after 1 week of treatment was shown to be an independent factor for predicting severe Hb drop (≥3 g/dL) at 4 weeks (P < 0.0001), and dose reduction of ribavirin during treatment (P = 0.0321). Conclusion: Early elevation of serum bilirubin level was found to be a possible predictive marker of both a severe drop of Hb in the early phase of treatment and dose reduction of ribavirin.     

聚乙二醇干扰素加利巴韦林治疗慢性丙型肝炎疗效影响因素分析

目的研究聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎（丙肝）疗效的影响因素。方法101例慢性丙肝患者均给予聚乙二醇干扰素α-2a 180μg／周联合利巴韦林10．6～15．0mg／（kg·d）,疗程48周,分析性别、体重指数（body mass index,BMI）、初始HCVRNA定量、ALT及GLU等对持续病毒学应答（sustainedvirologicresponse,SVR）的影响。结果聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙肝总的SVR率为50％,其中获得快速病毒学应答（rapid virologic response．RVR）和早期病毒学应答（early virologic response,EVR）患者实现SVR达100％,未获得RVR和EVR患者实现SVR为19．35％;高BMI值、发生脂肪肝的患者不容易达到SVR,而糖化血红蛋白、初始HCVRNA载量高、GLU、ALT及性别对SVR无影响。结论RVR、EVR可以预测SVR;BMI、是否合并脂肪肝是聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙肝获得SVR的影响因素。     

Partial splenic embolization prior to combination therapy of interferon and ribavirin in chronic hepatitis C patients with thrombocytopenia

Aim: A low platelet count leads to dose reduction of interferon (IFN) and is associated with failure to achieve a sustained virological response (SVR) in chronic hepatitis C patients. However, partial splenic embolization (PSE) is effective for treating thrombocytopenia resulting from hypersplenism. Methods: We compared the clinical features of 10 patients receiving PSE prior to the combination therapy of IFN and ribavirin (RBV) (PSE group) with those of 10 non‐receiving PSE patients (non‐PSE group). Results: In all 10 patients, PSE was successfully performed without serious adverse events. After PSE, leukocyte, neutrophil, and platelet counts significantly increased. The period from PSE to the initiation of the combination therapy was 15 (7–21) days. In the PSE group, two of six patients (33%) infected with genotype 1, and all four patients infected with genotype 2, achieved SVR. In the non‐PSE group, only three patients infected with genotype 2 achieved SVR. Two patients in the PSE group and one in the non‐PSE group discontinued the combination therapy. Three patients of the PSE group and five of the non‐PSE group reduced the dose of pegylated IFN‐α‐2b because of thrombocytopenia. In the PSE group, platelet counts during the combination therapy fell to baseline levels; however, they did not fall to lower levels than baseline levels. In the non‐PSE group, platelet counts 1 month after the initiation of the therapy were lower than baseline levels. Conclusion: The increase of platelet counts after PSE may allow the safe use of IFN and RBV and improve the SVR rate in chronic hepatitis C patients with thrombocytopenia.     

复发和无应答慢性丙型肝炎患者再治疗的临床疗效分析

目的观察既往治疗后复发和无应答的慢性丙型肝炎患者再治疗的疗效,并分析可能影响疗效的因素。方法采用开放性、前瞻性队列研究。入组复发无应答患者,给予聚乙二醇干扰素（PEG-IFN）α-2a 180μg/周联合利巴韦林10.6～15 mg.kg-1.d-1治疗。无应答组27例,疗程为72周;复发组18例,疗程为48周;动态留取血清,进行血常规、肝功能和HCV RNA的检测,以分析疗效及相关影响因素。结果复发组和无应答组患者快速病毒学应答（RVR）分别为55.6%和25.9%（P=0.045）,完全早期病毒学应答（cEVR）分别为83.3%和51.9%（P=0.031）,治疗结束时病毒学应答率（ETVR）分别为83.3%和59.3%（P=0.087）。基线HCVRNA在复发组低于无应答组,同时获得病毒学应答组（RVR、cEVR、ETVR）基线HCV RNA也均低于未获得病毒学应答组（仅cEVR节点有统计学意义,P=0.039）;复发组病毒动力学呈快速下降,无应答组病毒动力学呈缓慢下降;获得病毒学应答（RVR、cEVR、ETVR）组基线淋巴细胞百分比（LYPH%）均高于未获得病毒学应答组（P=0.009、0.037、0.020）。结论复发和无应答慢性丙型肝炎患者再治疗后,复发组近期疗效（RVR、cEVR、ETVR）优于无应答组;基线HCV RNA低、病毒动力学快速下降型及基线较高水平LYPH%是疗效的阳性预测因素。