Individualized treatment of hepatitis C virus infection

The current treatment of chronic hepatitis C since several years, the association of pegylated interferon and ribavirine, allows to obtain a virological eradication in around 55% of patients, including 45% of those infected with the genotype 1. The cure, defined by an undetectable viremia 24 weeks after the discontinuation of treatment, is associated to an improvement of the prognosis of the patients with a decrease of mortality and morbidity. If the virologic recovery allows fibrosis regression, including cirrhosis reversal, why not to treat every HCV-infected patient? Because first therapy is not mandatory in all the patients (minim liver disease, co-morbidities which may be contraindications to therapy), second adverse events are frequent and may be severe, third costs are high (the antiviral treatment but also hematological growth factors…) and finally the treated patients do not recover constantly. This has resulted in personalized therapies based on the severity of the disease, the early viral kinetics, pharmacologic monitoring, genetic and immunological factors. In addition to these factors of personalization, the development of new anti-viral C molecules, the protease inhibitors (boceprevir or telaprevir which are about to be approved in combination with pegylated interferon and ribavirine) will allow to achieve a sustained virologic response in around 75% of cases.     

Histological Benefit of Retreatment by Pegylated Interferon Alfa-2b and Ribavirin in Patients with Recurrent Hepatitis C Virus Infection Posttransplantation

We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin in patients who did not respond to previous posttransplant recurrent HCV treatment with IFN/ribavirin combination. Twenty-seven patients were consecutively included in this study and retreated with pegylated interferon alfa-2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21 untreated patients enrolled during the same period. Primary endpoint was the SVR and secondary endpoint was histological evaluation 24 weeks after ending therapy. Twenty-seven patients started therapy but 2 (7%) stopped because of side effects. On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02) were significantly associated with viral clearance. In 46 patients in whom paired graft biopsies were available, fibrosis score was improved in 76% of treated patients versus 5% in untreated patients. Among treated patients, improvement of fibrosis was not correlated to SVR. Our data show that 30% of patients who have failed prior posttransplantation treatment achieved an SVR when retreated with pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score was improved in 65% of treated patients despite failure of HCV eradication.     

Single nucleotide polymorphisms near IL28B gene and response to treatment of chronic hepatitis C in hemodialysis patients

Abstract

Background: It has been shown that single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) gene were associated with sustained virological response following standard antivirological treatment of chronic hepatitis C. Objectives: The aim of the study was to evaluate the association between SNPs near the IL28B gene and response to the treatment of chronic hepatitis C in hemodialysis patients. Patients and methods: The study group included 24 hemodialysis patients with chronic hepatitis C routinely treated with pegylated interferon α-2?a. HCV genotype 1 was the cause of chronic hepatitis C in all study participants. Sustained virological response was determined by an assay with a sensitivity of 20?IU/mL, 6 months after completion of the antivirological treatment. The genotyping of the three most widely studied IL28B gene polymorphisms (rs12979860, rs8099917, and rs12980275) was performed in all study participants. Results: Sustained virological response was achieved in 50% of the treated patients. The treatment response was significantly associated with the CC genotype of rs12979860, TT genotype of rs8099917, and AA genotype of rs12980275 (p?=?0.003, p?=?0.009, and p?=?0.012, respectively). Conclusions: The three most widely studied SNPs near the IL28B gene were associated with sustained virological response following antivirological treatment of chronic hepatitis C in hemodialysis patients.     

慢性丙型肝炎干扰素个体化治疗的临床观察

目的：观察不能耐受标准剂量干扰素治疗方案的部分丙型肝炎患者干扰素个体化给药的疗效,探索不同剂量干扰素治疗丙型肝炎的方法。方法收集多种原因不能耐受标准剂量干扰素治疗方案的丙型肝炎患者共28例,给予个体化低剂量干扰素（普通干扰素0.8～3 MIU/d,隔日1次）联合利巴韦林0.6～0.9 g/d治疗,疗程48周。结果89.29%（25/28）患者可耐受低剂量干扰素联合利巴韦林长期治疗。不同时间节点的病毒学应答率为：4周病毒学应答率（RVR）为7.04%,12周病毒学应答率（EVR）为17.85%、24周病毒学应答率53.85%、48周病毒学应答率为60.00%。停药后24周病毒学应答率（SVR）为48.00%。结论抗丙型肝炎病毒治疗可以改善肝功能,从而提高患者对高效抗逆转录病毒治疗的耐受性。     

国产聚乙二醇化重组集成干扰素变异体联合利巴韦林治疗慢性丙型病毒性肝炎患者甲状腺功能异常及其对疗效的影响

目的观察国产聚乙二醇化重组集成干扰素变异体注射液（PegIFN-SA）联合利巴韦林（RBV）治疗慢性丙型病毒性肝炎（CHC）患者时甲状腺功能异常（TD）或甲状腺自身抗体（TAs）产生情况及对疗效影响。 方法前瞻性观察2013年9月至2015年12月于本中心接受国产PegIFN-SA联合RBV治疗的CHC病例45例。试验组患者给予PegIFN-SA皮下注射（1.5 μg/kg、1次/周）,对照组患者给予聚乙二醇化干扰素α-2a（PegIFN-α-2a）皮下注射（派罗欣180 μg、1次/周）,两组患者均联合口服利巴韦林（000~1 200 mg/d）,HCV基因2、3型患者治疗24周,非HCV基因2、3型患者治疗48周,停药后均随访6个月。在治疗前、治疗后每3个月及停药后6个月监测两组患者甲状腺功能及HCV RNA水平。 结果试验组慢性丙型肝炎患者30例,其中男性14例,女性16例,平均年龄为（36.5 ± 12.0）岁（19~56岁）,HCV基因2、3型患者6例,HCV非基因2、3型患者24例。治疗结束停药半年后HCV持续应答率为83.3%（25/30）,共13例患者出现TD或TAs,其发生率为43.3%（13/30）;9例发生TD患者中4例（44.4%）丙型肝炎复发,高于未出现TD者（1/21,4.8%）,差异具有统计学意义（P = 0.02）。 结论国产PegIFN-SA联合RBV治疗慢性丙型病毒性肝炎患者甲状腺功能异常及抗体阳性较为常见,发生甲状腺功能异常者CHC更易复发。     

聚乙二醇化干扰素联合利巴韦林治疗慢性丙型肝炎疗效的影响因素

目的探讨聚乙二醇化干扰素（PegIFN）联合利巴韦林（RBV）治疗慢性丙型肝炎疗效的影响因素。 方法回顾性分析2008年1月至2011年12月于宝鸡市中心医院接受PegIFN和RBV联合治疗的148例HCV感染者的临床资料。采用持续性病毒应答24周（SVR24）、早期病毒学应答（EVR）、治疗结束病毒应答（ETR）、持续性病毒应答12周（SVR12）、复发、无效应答、病毒学突破评估疗效,Logistic回归分析影响疗效的因素。 结果148例HCV感染者失访12例（8.1%）。136例HCV感染者中128例（94.1%）患者出现EVR、118例（86.8%）患者出现ETR、114例（83.8%）患者出现SVR12、112例（82.4%）患者出现SVR24、8例（5.9%）患者无效应答、6例（4.4%）患者复发、4例患者出现病毒学突破（2.9%）。HCV RNA、HCV基因型和UA均为影响HCV感染者SVR24的因素（P均< 0.05）。 结论PegIFN联合RBV治疗HCV感染疗效显著。HCV基因型2/3、HCV RNA水平较低和尿酸与HCV SVR相关。     

Sustained virologic response to therapy of recurrent hepatitis C after liver transplantation is related to early virologic response and dose adherence.

Sustained virologic response (SVR) after antiviral therapy for recurrent hepatitis C virus (HCV) infection in liver transplant (LT) recipients is consistently lower than that achieved in non-LT patients. We evaluated efficacy and safety of pegylated interferon (IFN) and ribavirin (RBV) therapy in LT recipients with recurrent HCV and factors associated with SVR. All subjects with histologic evidence of recurrent HCV were intended to be treated for 48 weeks with full-dose pegylated IFN; target dose of RBV was 800 mg/day. Thirty-five LT recipients with recurrent HCV, median age 48.5 years, 77% genotype 1, and median pretreatment HCV RNA 6.4 log10 IU/mL were treated between January 2000 and February 2006. Antiviral therapy was discontinued prematurely in 15 subjects as a result of adverse events. Median overall treatment duration was 46 weeks. Early virologic response at week 12 was seen in 17 (49%) and an end-of-treatment virological response in 19 (54%) patients. SVR was achieved in 13 patients (37%), and all 9 patients followed for >1 year after treatment had durable response. Patients with SVR had significantly lower pretreatment HCV RNA (5.7 vs. 6.5 log10 IU/mL, P=0.003), more likely to have a week 12 virological response (85% vs. 27%, P=0.0009) and received higher cumulative doses of pegylated IFN (75% vs. 33%, P=0.029) and RBV (90% vs. 26%, P=0.016) compared with patients whose disease did not respond to therapy. In conclusion, SVR was achieved in 37% of patients with recurrent hepatitis C after LT. Similar to non-LT patients, those with lower pretreatment HCV RNA, a week 12 virological response, and pegylated IFN and RBV dose adherence were more likely to achieve SVR.     

A Pilot Study: Longer Duration of Posttransplant Hepatitis C Virus Therapy May Increase the Sustained Response Rate

Background

Although end of treatment virological responses are similar in posttransplant patients with recurrent chronic hepatitis C virus infection and nontransplant patients, the sustained virological response rate is lower in the posttransplant setting. We investigated the efficacy of a longer duration (3 years) of therapy.

Methods

Thirteen patients with biopsy-proven recurrent hepatitis C were included in the study. In the first year of therapy, all patients were treated with a standard regimen of interferon alpha 2b 3MU 3 times in a week plus ribavirin (800 to 1000 mg/d). After the availability of pegylated interferon, patients were converted to pegylated interferon (1.5 μg/kg body weight). Hepatitis C virus RNA was evaluated at months 3, 6, 9, 12, 24, 36, and 42. If hepatitis C virus RNA was negative at month 12, the patients continued treatment for 36 months.

Results

Hepatitis C virus RNA was negative in six patients at 12 months, including two who became hepatitis C virus RNA negative after 3 months; two, after 6 months; and two, after 12 months of therapy. Those six continued treatment completing 3 years of treatment with a sustained virological response. Four of those six patients with sustained virological response required colony-stimulating factors during treatment.

Conclusion

Although the hepatitis C virus RNA status of patients at 12 weeks is a good marker to predict a sustained virological response in the nontransplant setting, it is not valid in posttransplant patients. A prolonged duration of therapy for patients who are viral responders at 12 months may prevent recurrence and increase the sustained virological response rate.     

肝移植后丙型病毒性肝炎复发治疗时获得持续病毒应答的影响因素

目的 探讨聚二乙醇干扰素治疗肝移植后丙型病毒性肝炎复发的效果,分析影响产生持续病毒应答率(SVR)的因素.方法 将肝移植后丙型病毒性肝炎复发并使用聚乙二醇干扰素α-2a进行抗丙型肝炎病毒(HCV)治疗的39例患者纳入研究,其中有21例因为抗HCV治疗无效或发生不良反应而中途停药,其余18例接受了全疗程规范治疗.18例患者中,男性13例,女性5例,平均年龄54岁(27～67岁),疗程25～105周.治疗后4、12、24周,病毒转阴后24周及停药后24周,检测HCV RNA的复制水平.停药后24周HCV RNA复制持续阴性为产生SVR.对患者年龄,性别,治疗前HCV RNA水平,HCV基因型,是否获得早期病毒应答(EVR),治疗前血清AST水平等因素与获得SVR的相关性进行分析.结果 有4例(22.2%)患者获得了SVR,其平均治疗周期为57周.经统计分析显示,HCV基因型为非1B型(P=0.023),治疗前HCV RNA载量＜106拷贝/ml(P=0.044),以及获得EVR(P=0.019)等3个参数与获得SVR密切相关.结论 HCV基因型为非1B型、治疗前低水平HCV RNA复制和获得EVR可作为肝移植后丙型病毒性肝炎复发抗HCV治疗疗效的有效预测因子.

Abstract：

Objective To investigate the efficacy of pegylated interferon (Peg-IFN) plus ribavirin to treat hepatitis C virus (HCV) recurrence, and analyze possible factors associated with sustained viral responses (SVR). Methods The enrolled 39 patients, who had recurrence of hepatitis C after liver transplantation and received antiretroviral therapy, were analyzed. Treatment was discontinued in 21 patients due to side effects, and the remaining 18 patients [13 males, 5 female,median age of 54 (27-67) years, treatment duration of 25-105 weeks)] were subjected to whole standard treatment. During the treatment, HCV RNA was measured at 4, 12, 24, and 24 weeks after HCV negative change as well as drug withdrawal. SVR was defined as HCV RNA negativity within 24 weeks after the drug withdrawal. The following variables were analyzed: ages, gender,pretreatment viral load, genotype, early viral response (EVR), levels of alanine aminotransferase before treatment and their association with SVR. Results The mean treatment duration was 57weeks with an SVR achieved in 4/18 (22. 2 %). Statistical analysis revealed that the genotype of non1B (P=0.023), RNA ＜106 copy/ml (P= 0. 044) before treatment and EVR (P=0.019) were the variables associated with SVR. Conclusion Genotype of nor-1B, low level RNA before treatment and EVR were the effective predictors of interferon antiviral therapy for recurrent hepatitis C after liver transplantation.     

Pegylated interferon-α-based treatment for chronic hepatitis C in renal transplant recipients: an open pilot study

Treatment of hepatitis C in renal transplant recipients remains a controversial issue, as interferon therapy has been associated with a high risk of rejection and poor efficacy. We report here the use of pegylated interferon-α, alone or in combination with ribavirin, in renal transplant recipients with chronic hepatitis C. Eight renal transplant recipients with chronic hepatitis C were recruited. The mean delay between renal transplantation and antiviral therapy was 198.8 months. Sustained virological response was observed in four of out eight patients. Three patients with sustained virological response were genotype 2, one was genotype 1; fibrosis stages were F1 for one patient, F2 for 2, F3 for one. At baseline, renal dysfunction was moderate in seven patients and severe in one patient. No patient experienced rejection episodes during or after pegylated interferon-α therapy. One patient developed haemolytic uraemic syndrome, which eventually resulted in graft loss and return to dialysis. In conclusion, for renal transplant recipients treated with pegylated interferon-α-based therapy, we observed a low risk of renal dysfunction, acceptable tolerance and significant virological efficacy. This is therefore the first study to suggest that pegylated interferon-α could be proposed late after transplantation to renal transplant recipients.     

Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis C after liver transplantation

Recurrent hepatitis C is often treated with an interferon and ribavirin combination therapy, but the results have been disappointing. Given the promising results reported with pegylated interferon and ribavirin for hepatitis C, we were interested in evaluating the effectiveness of this treatment in liver transplant recipients with recurrent hepatitis C (HCV). METHODS: Between November 2001 and September 2002, patients with recurrent HCV were screened to determine if they were eligible for treatment. Liver function tests, HCV-RNA, and liver biopsies were performed on all patients prior to treatment. HCV-RNA was repeated at 3 months, the end of treatment (EOT), and 6 months after EOT for patients who were HCV-RNA negative at EOT. Patients were prospectively followed after starting weekly pegylated interferon alfa-2b 1.5 mcg/kg per week and ribavirin 800 mg per day (Schering-Plough, Kenilworth, NJ, USA) with folic acid 1 mg per day. RESULTS: Thirty-nine patients eligible for treatment displayed a median age of 50.4 years. Eighteen patients completed treatment, 4 remain on treatment, and 17 were intolerant. Sustained HCV-RNA eradication occurred in 66.7% of patients who completed treatment. Side effects led to treatment withdrawal in 17 patients (43.6%) In an intention-to treat analysis, sustained HCV-RNA eradication occurred in 30.8% of patients. CONCLUSION: Side effects are an important limiting factor in the treatment of recurrent HCV with pegylated interferon and ribavirin. However, these results are encouraging as sustained HCV eradication occurred in at least 66.7% of patients who completed treatment. Prospective randomized trials are required to assess the effectiveness of this treatment and its impact on quality of life and histology.     

Randomized trial of pegylated interferon alpha-2b monotherapy in haemodialysis patients with chronic hepatitis C.

BACKGROUND: Chronic hepatitis C infection is prevalent among haemodialysis patients. The goal of our study was to determine the efficacy and safety of pegylated interferon alpha-2b in haemodialysis patients with chronic hepatitis C. METHODS: We conducted a trial which randomized haemodialysis patients with chronic hepatitis C to 1.0 or 0.5 microg/kg of pegylated interferon alpha-2b subcutaneously, weekly for up to 48 weeks. End-points were sustained viral response and adverse events. Data were analysed as intention to treat and as intended per protocol. RESULTS: After 16 patients were enrolled, the study was terminated because of adverse events and modifications needed in the study design. Nine subjects were randomized to the 1.0 microg/kg group and seven subjects were randomized to the 0.5 microg/kg group. Serious adverse events requiring discontinuation of therapy occurred in five (56%) subjects in the 1.0 microg/kg group and in two (28%) subjects in the 0.5 microg/kg group (P = 0.36). The most common adverse events were hypertension and infection unrelated to neutropenia. Two (22%) subjects in the 1.0 microg/kg group, both genotype 1, had a sustained viral response, and none of the subjects in the 0.5 microg/kg group had a sustained viral response (P = 0.47). Five subjects in the 1.0 microg/kg group were able to complete 24 weeks or longer of therapy as per protocol and two (40%) were sustained responders. CONCLUSIONS: In our study group, pegylated interferon alpha-2b was poorly tolerated and was associated with substantial side effects. Sustained response rates seen with pegylated interferon in our study do not appear to be better than rates reported for standard interferon alpha-2b.     

Pegylated Interferon Alpha-2b for Patients with HCV Recurrence and Graft Fibrosis Following Liver Transplantation

Chronic hepatitis C is a principal indication for liver transplantation. Recurrent viral infection is inevitable and graft disease is common. We report tolerability, safety and efficacy of pegylated interferon alpha 2b (PEG-IFN) monotherapy for patients with hepatitis C virus (HCV) recurrence and fibrosis after liver transplantation. Repeated measurements of serum HCV titer permitted assessment of the kinetics of the antiviral response for all patients. We screened 63 patients transplanted for HCV at our center for antiviral treatment, 14 were eligible and treated, but only 6 completed the proposed 52 weeks of therapy. Eight were withdrawn because of severe/life-threatening side effects/events, including liver dysfunction (4 patients). None of those 8 achieved a sustained virological response (SVR). Five of 6 who completed treatment were HCV RNA negative at the end of treatment, and 2 achieved an SVR. Viral kinetics were similar to published observations for treatment of non-transplanted HCV patients. Patients with genotype non-1 infection displayed a more rapid decline of viral titer than was observed for genotype 1 infection. Post-transplant HCV patients are frequently unsuitable for, or intolerant of PEG-IFN. Liver dysfunction was a major concern.     

Pegylated interferon alpha-2a for treatment of chronic HCV infection in hemodialysis patients: a single Saudi center experience

Introduction

Chronic hepatitis C infection is common among patients on dialysis. While the associated liver disease is usually relatively mild during dialysis, disease progression can accelerate due to immunosuppression following kidney transplantation, and interferon therapy after transplantation stimulates graft rejection. Pegylated interferon and ribavirin are now the recommended treatment for chronic hepatitis C virus in patients without renal failure. However, until now, there has been relatively little information on the efficacy and tolerability of pegylated interferon in dialysis patients.

Aim of the work

To evaluate the response to pegylated interferon alpha-2a in chronic hepatitis C?Cinfected patients on chronic hemodialysis.

Patients and methods

This controlled study included 28 patients with end-stage renal disease who had been on dialysis in the Prince Salman Center for Kidney Disease for more than 6 months and tested positive for HCV RNA on repeated occasions. Thirteen patients were treated with pegylated interferon alpha-2a therapy (of which three were also receiving ribavirin), and the remaining fifteen served as controls. Viral genotyping and both qualitative and quantitative PCR were carried out before starting therapy. Treatment was continued for 48 weeks. After 24 weeks of treatment, the biochemical and virological responses were evaluated. Biochemical response was evaluated at the end of the treatment, with sustained virological response (SVR) being evaluated 24 weeks later. The side effects were monitored throughout the treatment period.

Results

All patients in the treatment group completed 48 weeks of therapy without any drop out. Their mean age was 43.38 ± 11.62 years. After 24 weeks of therapy, 10 patients (76%) were initial responders, while 3 patients (24%) were resistant. Six months after termination of therapy, 9 patients (69%) were sustained responders, while one patient relapsed. Their ALT and AST dropped from 55.78 ± 33.79 IU/dl and 34.04 ± 19.58 IU/dl before starting therapy to 27.22 ± 16.54 IU/dl and 18.88 ± 12.28 IU/dl after termination (P = .06 and .08, respectively). Their mean hemoglobin (Hb) level dropped from 11.05 ± 1.43 to 9.48 ± 1.24 g/dl (P = 0.3), and white blood cell count (WBC) dropped from 6.82 ± 2.6 × 10³/mm³ to 4.1 ± 2.34 × 10³/mm³; (P = 0.57). Platelet count fell from 194.56 ± 129.78 × 10³/mm³ to (152.33 ± 107.66 × 10³/mm³; P = 0.39). When initial responders (n = 10) were compared to resistant patients (n = 3), the only observable difference was higher ALT and AST levels in resistant patients. Pegylated interferon alpha-2a was well tolerated, and none of the patients stopped interferon because of hematological side effects while dose modification was carried out in most of the patients. All three patients who received combination therapy from the start were sustained responders. None of the patients in the control group seroconverted to HCV negative status during the study period.

Conclusion

Pegylated interferon alpha-2a was well tolerated among our hemodialysis patients. Hematological disturbances appeared to be the most important adverse effects. At the end of therapy a response rate of up to 76%, with 69% sustained response, can be obtained with pegylated interferon alpha-2a therapy.     

Effective Treatment With Daclatasvir and Asunaprevir in Kidney Transplant Patients Infected With Hepatitis C Virus: A Report of Two Cases

Background

Hepatitis C virus (HCV) infection is known to affect long-term patient and graft survivals after kidney transplantation (KT). Recently, combination therapy with the use of 2 oral direct-acting antivirals, daclatasvir (DCV) and asunaprevir (ASV) reportedly showed a high rate of HCV eradication. We report the safety and efficacy of DCV and ASV therapy in 2 KT patients.

Preemptive therapy with pegylated interferon alpha-2b and ribavirin after liver transplantation for hepatitis C cirrhosis

We present our results of preemptive treatment with pegylated interferon and ribavirin after liver transplantation for hepatitis C cirrhosis. PATIENTS: Between September 2001 and August 2002, four patients were started on combination therapy with pegylated interferon-alpha-2b (1microg/kg weekly) and ribavirin (400-1000 mg/d) 3 to 4 weeks' posttransplant. Treatment was continued for 6 (genotype 3a, 2 patients) or 12 (genotype 1b, 2 patients) months. Virologic and biochemical responses as well as side effects were evaluated. RESULTS: Two patients (genotype 3a) became HCV (hepatitis C virus)-RNA negative after 3 months of therapy and are persistently negative 20 and 14 months after end of therapy. One patient (genotype 1b) became HCV-RNA negative 6 months after start of treatment, but therapy had to be withdrawn after 9 months owing to fatigue and suspicion of angina pectoris. One patient who was later retransplanted because of hepatic artery thrombosis discontinued therapy after 2.5 months owing to anemia, leukopenia, and no signs of HCV-RNA reduction. Interestingly, two of the responders were nonresponders prior to liver transplant. Median ALT levels at start of therapy were 98 U/L (r = 60-126) and 12 months later 40 U/L (r = 24-58) (n = 4). No rejection episode was detected. CONCLUSION: In patients liver-transplanted due to HCV-cirrhosis, combination therapy with pegylated interferon and ribavirin can be effective and safe in the early posttransplant period, thus preventing recurrent hepatitis C.     

Recurrent hepatitis C after liver transplantation: on-treatment prediction of response to peginterferon/ribavirin therapy.

Sustained virologic response (SVR) in the treatment of recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) remains suboptimal. We evaluated efficacy of pegylated interferon alfa (PEG) and ribavirin (RBV) (PEG/RBV) combination therapy in LT recipients with recurrent HCV and predictive values of rapid virological response (RVR) and early virologic response (EVR). Between January 2001 and October 2005, LT recipients with recurrent HCV were intended to be treated for 48 weeks with PEG/RBV combination therapy independent of genotype or virologic response [53 patients (79% genotype 1)]. On-treatment predictor of response at week 4 (RVR) was defined as undetectable HCV RNA, and at week 12 (EVR) as undetectable HCV RNA or a >2 log(10) drop from pretreatment viral load. SVR was seen in 19 (35%) patients. Patients with genotype 2/3 were more likely to achieve SVR than those with genotype 1 (87% versus 23%; P = 0.001). The highest rate of SVR was seen in patients with RVR [specificity and positive predictive value (PPV) = 100%] while the highest rate of treatment failure was seen in those who did not have EVR [sensitivity and negative predictive value (NPV) = 100%]. The NPV of RVR to identify those who will not achieve SVR was also very high (88%). EVR had low PPV (63%) to identify those with SVR. In conclusion, PEG/RBV combination therapy is effective in the treatment of post-LT recurrent HCV. On-treatment virologic monitoring is highly predictive of SVR and may optimize the virologic response and minimize toxicity. Given its high PPV and NPV, RVR appears to be the most appropriate decision time point for continuation of therapy.     

IL-28B单核苷酸基因多态性与CHB干扰素疗效的相关性

目的：探讨IL-28B单核苷酸基因多态性与慢性乙型肝炎（CHB）干扰素疗效的相关性。方法选取300例HBeAg阳性CHB患者，给予聚乙二醇化干扰素α（Peg-INF-α）规范治疗48周后以PCR法对IL-28B SNP rs12979860及IL-28B SNP rs8099917基因分型进行检测。结果治疗后HBV DNA定量、ALT、AST水平明显较治疗前下降（P＜0.05），HBeAg转移率53.13%，随访1年后应答率49.44%；Peg-INF-α应答患者与非应答患者IL-28B SNP rs12979860基因型CC、CT、TT分布及等位基因C、T频率比较差异无统计学意义（P＞0.05），IL-28B SNP rs8099917基因型TT、TG分布及等位基因T、G频率比较差异具有统计学意义（P＜0.05）。结论 IL-28B SNP rs8099917可能对干扰素治疗的应答反应性形成影响，其中等位基因G的频率升高可能提示着干扰素的成功应答，因而检测IL-28B SNP rs8099917对干扰素治疗的CHB患者治疗疗效有一定预测价值。