Hepatitis C virus-RNA clearance in HIV-coinfected patients with chronic hepatitis C treated with pegylated interferon plus ribavirin

Hepatitis C virus (HCV)-RNA clearance seems to occur more slowly in HIV/HCV-coinfected patients than in HCV-monoinfected subjects treated with pegylated interferon alpha (peg-IFN) plus ribavirin (RBV). As a consequence, concern has arisen over the feasibility of following the treatment rules applied to HIV-negative patients with chronic hepatitis C. A total of 89 HIV/HCV-coinfected patients who had fully completed a course of peg-IFN plus RBV were analysed. Of these, 29 (32.6%) reached sustained virological response (SVR). Reductions >2 logs in plasma HCV-RNA occurred in 52 (58%) patients at week 12 of treatment (early virological response; EVR). None of patients who showed HCV-RNA drops <2 logs at week 12 reached SVR (negative predictive value: 100%). The positive predictive value of EVR was 56%. On the other hand, relapses occurred in 19 (39.6%) out of the 48 patients who had negative HCV-RNA at the end of treatment, and there were no differences noted when comparing patients with HCV genotypes 2/3 and 1/4. In summary, the quantitative assessment of plasma HCV-RNA at week 12 predicts the chance of SVR using peg-IFN plus RBV in HIV-positive patients with chronic hepatitis C, as it does in HIV-negative individuals. Thus, discontinuation of anti-HCV therapy, which is associated with frequent side effects, might be warranted in HIV/HCV-coinfected patients showing HCV-RNA reductions <2 logs at week 12 of treatment. On the other hand, relapses in virological responders were unexpectedly high in HIV/HCV-coinfected patients when treatment was provided following the rules applied to HIV-negative subjects. This is particularly relevant for HCV genotypes 2/3, which only rarely relapse in HIV-negative patients. Therefore, extending therapy (for 12 months in HCV genotypes 2/3 and perhaps for 18 months in HCV genotypes 1/4) might be warranted in HIV/HCV-coinfected patients showing EVR.     

Response to interferon-based therapies in HIV-infected patients with chronic hepatitis C due to genotype 4

BACKGROUND: The hepatitis C virus (HCV) genotype is the main predictor of response to interferon (IFN)-based therapies. HCV genotype 4 is spreading among European intravenous drug users, who are frequently coinfected with HIV. Information about treatment response in this subset of patients is scarce and conflicting results have been reported. METHODS: All HIV-infected patients treated for chronic hepatitis C at our institution with a minimum follow-up of 6 months after discontinuing therapy were retrospectively analysed. They had received one of three HCV treatment modalities: IFN monotherapy, IFN plus ribavirin (RBV) or pegylated interferon (PEG-IFN) plus RBV. Treatment responses were stratified according to HCV genotype. RESULTS: A total of 390 patients were analysed. Sustained virological response (SVR) to HCV therapy had been reached by 90 (23.1%): 22/119 (18.5%) with IFN monotherapy; 17/106 (16%) with IFN plus RBV; and 51/165 (30.9%) with PEG-IFN plus RBV. SVR was significantly higher among those with HCV genotypes 2 or 3 (40.4%; 61/151) than in patients with either HCV genotype 1 (11.2%; 22/197) or HCV genotype 4 (16.7%; 7/42) (P<0.0001). In contrast, there were no significant differences in the response rate comparing HCV genotypes 1 and 4 (P=0.53). CONCLUSIONS: Response to IFN-based therapies in HIV-positive patients with hepatitis C due to HCV genotype 4 is poor, similar to that obtained for HCV genotype 1 and much lower than for HCV genotypes 2 and 3. Therefore, HIV-infected patients with hepatitis C due to genotype 4 should be considered as a particular subset of difficult-to-treat patients. New treatment strategies and drugs for these patients are eagerly awaited.     

Response to combined interferon and ribavirin is better in patients infected with hepatitis C virus genotype 6 than genotype 1 in Hong Kong

Data on the treatment efficacy of interferon (IFN)-alpha and ribavirin in patients with chronic hepatitis infected with hepatitis C virus (HCV) of genotype 6 are lacking. A study has been reported from Hong Kong which compared the treatment efficacy of IFN-alpha and ribavirin in the treatment of chronic HCV infection with genotypes 1 and 6. Twenty-four patients with HCV genotype 1 and 16 patients with HCV genotype 6 were studied. The baseline demographic data including median age, gender ratio, alanine aminotransferase levels, bilirubin levels, HCV RNA levels and histological scores were comparable between the two groups of patients. All patients received IFN-alpha 5 million units three times per week and ribavirin (1,000 mg for those weighing 75 kg) for 1 year. Patients infected with HCV genotype 6 achieved virological response significantly higher than those with HCV genotype 1 (67 vs. 33% at week 24, p = 0.02; 75 vs. 42% at the end of treatment, p = 0.05; 63 vs. 29% at 6 months after completion of treatment, p = 0.04). Histological improvement in inflammatory activity and fibrosis in the liver were observed in 25% and 25% of patients infected with HCV genotype 6 in contrast to only 13 and 8% in patients infected with HCV genotype 1; however, the differences were not statistically significant. In conclusion, patients with HCV genotype 6 gain a better response to combined treatment with IFN-alpha and ribavirin than those with HCV genotype 1 and achieve a significantly higher rate of sustained virological response.     

Genotype does not affect pattern of HCV RNA decrease among responders during interferon treatment of chronic hepatitis C. Consensus Interferon Study Group

We assessed differences in the pattern of HCV RNA decrease for HCV genotypes 1, 2, and 3 during interferon treatment to determine if the lower response rates observed among genotype 1 patients were related to a slower decrease in HCV clearance. Serum HCV RNA values of 472 chronic hepatitis C patients treated with either consensus interferon (CIFN) or interferon alfa-2b (IFN alfa-2b) were evaluated. Neither virological sustained responders nor relapsers differed in the pattern of serum HCV RNA decrease based on genotype. Virological sustained responders infected with genotype 1 cleared HCV RNA as rapidly as sustained responders who were infected with genotype 2 or 3. Relapsers had a slower rate of serum HCV RNA decrease than did virological sustained responders. Nonresponders differed in the pattern of serum HCV RNA decrease based on genotype: HCV genotype 3 patients had the greatest decrease in serum HCV RNA; genotype 2 patients had an intermediate decrease; and genotype 1 patients had the least serum HCV RNA decrease. HCV genotype 1 patients treated with CIFN had a greater decrease in serum HCV RNA during therapy than did patients treated with IFN alfa-2b. However, there was no difference in the magnitude of serum HCV RNA decrease between the two interferon treatments for patients infected with genotype 2 or 3. In summary, both genotype and ultimate response to treatment are determinants of the pattern and rate of serum HCV RNA change during interferon therapy of chronic hepatitis C.     

Retreatment of patients with chronic hepatitis C not responding to interferon/ribavirin combination therapy with daily interferon plus ribavirin plus amantadine

There is currently no accepted therapeutic regimen for patients with chronic hepatitis C who failed to respond to standard combination treatment with interferon-alpha plus ribavirin. We investigated triple combination treatment with induction dosing of interferon-alpha plus ribavirin plus amantadine in these difficult-to-treat patients. Nonresponders (n = 67), breakthroughs (n = 16) and relapsers (n = 19) to previous interferon/ribavirin combination treatment of at least 6 months were included. For the first 16 weeks, patients received interferon-alpha2a 6 MU daily, ribavirin 800-1200 mg/d, and amantadine 200 mg/d. In cases of undetectable HCV RNA at week 12, treatment was continued with interferon-alpha2a 6 MU every other day and the same doses of ribavirin and amantadine until week 48. In cases of HCV RNA positivity at week 12, treatment was stopped. A total of 102 patients were enrolled (80%: genotype 1, 19%: cirrhosis). HCV RNA was negative in 35/102 patients (34%) at week 12 and in 27/ 102 patients (26%) at the end of treatment. Virological response was sustained in 15/102 patients (15%). On-treatment virological response was higher in previous relapsers/breakthroughs than in previous nonresponders (week 12: 49% vs. 27%, p < 0.05; week 48: 46% vs. 16%, p < 0.01) but no such difference was found for sustained virological response (20% vs. 12%, NS). In conclusion, triple combination treatment with daily interferon-alpha plus ribavirin plus amantadine for 3 months can induce virological response in a considerable number of nonresponders/relapsers to previous dual combination treatment, but the sustained virological response rate remains low.     

Viral etiology of hepatocellular carcinoma and HCV genotypes in Taiwan

Etiologic variations of hepatocellular carcinoma (HCC) exist in different geographic areas of the world. Hepatitis B virus infection is associated with HCC. However, hepatitis C virus (HCV) infection plays an increasingly more important role in the development of HCC and is associated with more than 30% of HCC in Taiwan. The prevalence of HCV infection and HCV genotypes vary in different geographic areas. The prevalence of HCV genotype 1b (HCV-1b) was around 50-70% in Taiwan and even varied in different townships. In addition to host factors, HCV genotypes may be associated with the development of HCC. In our study, the prevalence of HCV-1b in patients with HCC was significantly higher than in those with liver cirrhosis and chronic hepatitis; multivariate analysis revealed that the disease severity was significantly correlated with age and HCV-1b. Furthermore, HCV-1b was associated with a lower response rate to interferon (IFN) therapy than HCV-2. Our study has demonstrated that mutations in the IFN sensitivity-determining region, spanning nucleotides 2,209-2,248 in the NS5A region, correlate with the sustained virological response to combination therapy with IFN and ribavirin in patients with chronic HCV-1b infection in Taiwan. A third-generation enzyme immunoassay for antibody to HCV can be used to predict viremia and monitor the virological response.     

Lack of rapid virological response predicts interferon-alpha2b/ribavirin therapy failure in HCV genotype 2 patients: a single-centre study

BACKGROUND: A minority of patients with HCV-2 chronic hepatitis does not attain a sustained virological response to interferon-based therapies. Registration trials have failed to identify the real proportion of HCV-2 non-responders, and predictors of non-response. The analysis of 'real-life' HCV-2 patients might help define the effectiveness of anti-HCV therapy and the role of response moderators. METHODS: A re-analysis of all treatment-naive HCV-2 patients who consecutively received weight-dosed ribavirin with either 3 MU three times a week standard interferon-alpha2b or 1.5 microg/kg/week pegylated interferon-alpha2b. RESULTS: The 94 interferon-treated patients and the 136 pegylated-interferon-treated patients were comparable for demography, prevalence of cirrhosis (25%) and adherence to therapy (74%). By intention-to-treat analysis, the overall sustained virological response rate was 80% (82% interferon versus 78% pegylated interferon). Overall, sustained virological rates were 83% for the 182 patients who cleared HCV RNA at week 4 (rapid virological response) and 52% for the 48 who did not (P < 0.001). The corresponding week 12 figures of HCV RNA clearance were 90% and 32%, respectively (P < 0.001). Sustained response was independent of gender, age, body mass index, modality of infection, duration and severity of liver disease, adherence to therapy and interferon type. After stratification for interferon type, the only treatment failure predictor was persistence of HCV RNA at week 4 and 12. CONCLUSIONS: Despite the prevalence of moderators of treatment outcome, HCV-2 patients showed as high sustained virological response rates as those reported in registration trials for HCV-2 and HCV-3 pooled patients; pegylated interferon therapy failure was predicted by lack of rapid virological response.     

Anticarcinogenic impact of interferon on patients with chronic hepatitis C: a large-scale long-term study in a single center

BACKGROUND: The anticarcinogenic capacity of interferon (IFN) was assessed in a cohort of Japanese patients with chronic hepatitis C en masse. PATIENTS AND METHODS: The rate of hepatocarcinogenesis was analyzed in 2,166 patients with chronic hepatitis C, of whom 1,654 had received IFN therapy while 512 had not. RESULTS: Crude rates of hepatocarcinogenesis in treated and untreated patients were 2.6 and 4.6% at the end of the 5th year, 5.8 and 12.7% at the 10th year and 13.9 and 23.9% at the 15th year (after completion of IFN therapy for those treated) (p < 0.001). IFN decreased the hazard ratio of carcinogenesis to 0.42 (p < 0.001) in multivariate analysis with adjustments for significant covariates including fibrotic stage, gamma-glutamyl transpeptidase level, gender, platelet count and age. Among the 1,654 patients treated with IFN, 606 (36.6%) achieved persistent loss of hepatitis C virus (HCV) RNA and an additional 266 (16.1%) gained normal levels of alanine aminotransferase without loss of HCV RNA for 6 months or longer after the completion of IFN therapy. Cumulative rates of hepatocarcinogenesis in sustained virological responders and biochemical responders were 1.4 and 2.0% at the end of the 5th year, 1.9 and 3.6% at the 10th year and 1.9 and 7.5% at the 15th year, respectively. The hazard ratio of sustained virological response was 0.10 (p < 0.001), and that of biochemical response was 0.12 (p < 0.001). Normalization of aminotransferase levels after IFN therapy without loss of serum HCV RNA decreased hepatocarcinogenesis. CONCLUSION: IFN significantly decreased the rate of hepatocarcinogenesis in patients with chronic hepatitis C as a whole in Japan, even in those who fail to clear HCV RNA from serum.     

Role of viral kinetics under HCV therapy in HIV/HCV-coinfected patients

Patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are less responsive to anti-HCV therapies and are at a higher risk of toxicity than HCV monoinfected patients. HCV viral kinetics is the basis for the study of response to interferon-based therapy and for predicting sustained virological response (SVR). A lack of early virological response (EVR; undetectable HCV RNA or a decrease of >/=2 log(10) from baseline) after 12 weeks of pegylated interferon (peg-IFN) plus ribavirin (RBV) is an equally reliable predictor of lack of SVR in HIV/HCV-coinfected patients and in the monoinfected HCV population. Early stopping rules are particularly important in coinfected HIV/HCV patients, considering their low chances of response in the more difficult-to-treat HCV genotypes 1 and 4 (<30%). Several factors have been involved in this low efficacy, including higher baseline HCV viraemia, slower viral kinetics decay under interferon pressure and a defective immune substratum. A better understanding of HCV viral kinetics under HCV therapy may be the basis for assaying different peg-IFN plus RBV schedules, such as induction or extending strategies, and may help physicians to make tailored decisions for the management of their patients.     

Sustained virological response following HCV therapy is associated with non-progression of liver fibrosis in HCV/HIV-coinfected patients

BACKGROUND: Chronic hepatitis C leads to progressive liver fibrosis, which is accelerated in HIV-coinfected patients. Unfortunately, hepatitis C virus (HCV) therapy provides sustained virological response (SVR) to only 40% of coinfected patients. Little is known about the regression of hepatic fibrosis in treated patients. METHODS: All coinfected patients who had completed a full course of HCV therapy at our institution were identified. Liver fibrosis staging was estimated using non-invasive procedures at the time of initiating HCV therapy and reassessed at the last patient's follow-up using elastometry (FibroScan). RESULTS: A total of 103 coinfected patients were identified. HCV genotype distribution was 1 (63%), 3 (29%) and 4 (8%). SVR had been attained by 34 individuals, while the remaining 69 were non-responders and/or relapsers. The mean lag time between the end of HCV therapy and the current assessment of liver fibrosis was 40 months, without differences between groups. Metavir score estimates were comparable before initiating HCV therapy in SVR and non-SVR patients. By contrast, current Metavir scores were lower in SVR than in non-SVR patients; for instance, F3-F4 estimates were 12% versus 54%, respectively (P < 0.001). Moreover, the longer the time elapsed after HCV therapy, the lower the liver fibrosis in SVR patients (rho = -0.39; P = 0.02). Conversely, liver fibrosis staging directly correlated with the lag following HCV therapy in non-SVR patients (rho = 0.25; P = 0.03). CONCLUSIONS: SVR after HCV therapy is associated with non-progression of liver fibrosis in HCV/HIV-coinfected patients, although this benefit may not be universal and improvement only been recognizable after several years of follow-up.     

Treatment of chronic hepatitis C in southern Taiwan

Chronic hepatitis C virus (HCV) infection may lead to cirrhosis and hepatocellular carcinoma. Interferon (IFN)-alpha is effective in the treatment of chronic hepatitis C. The rate of response to IFN is enhanced by increasing the IFN dose. Extending the treatment duration can reduce the relapse rate. Addition of ribavirin to IFN increases the sustained virological response (SVR). Thus, combination therapy with IFN and ribavirin was adopted for the treatment of chronic hepatitis C in Kaohsiung Medical University Hospital in 1998. Approximately 60% of patients receiving IFN/ribavirin therapy gained SVR. IFN 6 million units three times per week combined with daily ribavirin for 6 months achieved SVR more frequently than combination therapy with 3 million units. Factors for SVR in these combination regimens were HCV genotype, viral load and early virological response. Long-term follow-up of patients treated with IFN has shown that SVR might reduce the risk of progression to cirrhosis and hepatocellular carcinoma. Pegylated (peg)-IFN has a longer half-life and better efficacy. Combination therapy with peg-IFN and ribavirin accomplished higher SVR than conventional IFN and ribavirin. A multicenter clinical trial was conducted in Taiwan to compare the efficacy of combination therapy between peg-IFN/ribavirin and conventional IFN/ribavirin for 6 months. SVR was higher in patients receiving peg-IFN and ribavirin, especially in those infected with HCV genotype 1b. Based on the results obtained, the national health insurance started to sponsor the combination therapy in October 2003, with a suggested duration for 6 months. Some small-scale studies in Taiwan have postulated higher SVR for treatment duration of 12 than of 6 months in patients with genotype 1b. Further investigation should be conducted in the near future.     

氟伐他汀对合并高胆固醇血症的慢性丙型肝炎的抗病毒疗效的影响

目的：观察氟伐他汀对合并高胆固醇血症的慢性丙型肝炎的抗病毒疗效的影响。方法选取2006年9月至2008年9月合并高胆固醇血症慢性丙型肝炎60例,观察组30例,对照组30例,所有患者均予聚乙二醇干扰素α-2a＋利巴韦林治疗;观察组患者加用氟伐地汀;用药后4、12、24、36、48周及停药后12周、24周复查病毒RNA定量。结果氟伐他汀治疗合并高LDL血症的慢性丙型肝炎的患者的早期病毒学应答（EVR）、治疗结束时病毒学应答（ETVR）和持续病毒学应答（SVR）均显著高于对照组（53.3%vs.46.7%,85.1%vs.63.3%,81.5%vs.53.3%,P＜0.05）。结论氟伐他汀有利于提高合并高胆固醇血症的慢性丙型肝炎患者的抗病毒疗效。     

丙型肝炎病毒基因分型与治疗效果关系的研究

目的 分析丙型肝炎病毒（HCV）基因型与利巴韦林联合聚乙二醇干扰素α-2a治疗效果的关系,为临床抗HCV治疗提供依据.方法 选择179例慢性丙型肝炎初治患者进行利巴韦林联合聚乙二醇干扰素α-2a的标准方案进行治疗,采用实时荧光定量聚合酶链反应（PCR）进行HCV-RNA定量检测,采用基因测序检测进行HCV基因分型.治疗后评价持续病毒学应答（SVR）.结果 179例丙型肝炎患者中,HCV 1b型占79.3%,HCV 2a型占8.4%,HCV 3b型占5.0%,HCV 6a型占2.2%,HCV 1b、2a混合型占1.1%,其他型占4.0%.HCV 2a型患者获得SVR率明显高于HCV 1b型,差异有统计学意义（χ^2=4.956,P=0.026）.结论 该院HCV基因型主要为HCV 1b和HCV 2a型,HCV 1b型患者对标准治疗方案的疗效较2a型差.     

Combined interferon and ribavirin therapy for chronic hepatitis C in Taiwan

Chronic hepatitis C virus (HCV) infection, including its sequelae, is an important healthcare problem in Taiwan. The seroprevalence of HCV infection in first-time blood donors in Taiwan is 1.2% and an estimated 2-5% in the general population, with a great geographic variation. Genotype 1b is the most prevalent HCV genotype in Taiwan, with a prevalence rate of 50-70%. An increasing incidence of hepatocellular carcinoma (HCC) is mainly attributed to HCV infection, while the declining role of HBV is observed in Taiwan. The seroprevalence of hepatitis B surface antigen among patients with HCC was 90% three decades ago, while recently, chronic HCV infection accounts for more than 30% of HCC patients in the National Taiwan University Hospital. With the advent of a combined conventional interferon (IFN)-alpha and ribavirin therapy, to which Taiwan has contributed in the early study phase, the sustained virological response rate has been greatly improved compared with IFN monotherapy. The sustained virological response rate in Taiwanese patients treated with the combination therapy for 6 months has reached up to 50-60%, which is higher than that reported in patients from the Western countries receiving a 12-month regimen. It is necessary to search for the underlying mechanisms for the better treatment outcome with IFN plus ribavirin combination therapy in Taiwanese patients. Whether long-term effects of IFN plus ribavirin therapy can reduce the incidence of HCC needs to be established.     

Hepatitis C

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Here, we briefly review the virology, diagnosis and therapy of hepatitis C. Standard therapy with pegylated interferon-alpha and ribavirin results in a sustained virological response in 40-50% of genotype 1- and in about 80% of genotype 2- or 3-infected patients. Recent progress has allowed the identification of novel antiviral targets and therapeutic strategies. These will likely complement existing therapeutic modalities in the near future.     

Sustained virological response correlates with reduction in the incidence of glucose abnormalities in patients with chronic hepatitis C virus infection

OBJECTIVE: There is evidence to suggest that hepatitis C virus (HCV) infection is a high-risk condition for developing type 2 diabetes. However, there are no interventional studies that confirm that HCV infection causes diabetes. The main aim of this study was to compare the incidence of glucose abnormalities (diabetes plus impaired fasting glucose) between HCV-infected patients with or without sustained virological response (SVR) after antiviral therapy. RESEARCH DESIGN AND METHODS: Patients with normal fasting glucose (<100 mg/dl) with biopsy-proven chronic hepatitis C without cirrhosis and with at least 3 years of follow-up after finishing antiviral therapy were included in the study (n = 234). Patients received interferon alpha-2b (alone or with ribavirin) for 6 or 12 months according to genotype. Cumulative incidence of glucose abnormalities was evaluated by using the Kaplan-Meier method comparing subjects with and without a SVR to antiviral treatment. A multivariate Cox proportional hazards analysis was performed to explore the variables independently associated with the development of glucose abnormalities. RESULTS: During follow-up, 14 of 96 (14.6%) patients with SVR and 47 of 138 (34.1%) nonsustained responders developed glucose abnormalities (P = 0.001). Patients with SVR did not develop diabetes during follow-up, whereas nine cases of diabetes were detected in nonsustained responders (P = 0.007). After adjustment for the recognized predictors of type 2 diabetes, the hazard ratio for glucose abnormalities in patients with SVR was 0.48 (95% CI [0.24-0.98], P = 0.04). CONCLUSIONS: Our results provide evidence that eradication of HCV infection significantly reduces the incidence of glucose abnormalities in chronic hepatitis C patients. In addition, this study supports the concept that HCV infection causes type 2 diabetes.     

Long-term follow-up of HIV-infected patients with chronic hepatitis C virus infection treated with interferon-based therapies

BACKGROUND: Chronic hepatitis C virus (HCV) infection is frequent among HIV-infected patients. Clearance of serum HCV RNA 6 months after discontinuing HCV therapy is generally interpreted as a cure of HCV infection in HIV-negative subjects. However, the occurrence of liver complications (including hepatocellular carcinoma) and/or HCV relapses in coinfected patients when followed for long periods of time after HCV therapy is not well known. METHODS: All HIV-infected patients who had been treated for chronic hepatitis C at our institution and had a minimum follow-up of 6 months after discontinuing therapy were retrospectively analysed. They had received one of three HCV treatment modalities: IFN monotherapy, IFN plus ribavirin (RBV) or pegylated interferon (PEG-IFN) plus RBV. RESULTS: A total of 351 patients were retrospectively analysed. Sustained virological response (SVR) to HCV therapy had been reached by 77 (22%) of them: 22/119 (18.5%) with IFN monotherapy, 17/106 (16%) with IFN plus RBV and 38/126 (30.2%) with PEG-IFN plus RBV. Considering the HCV genotypes, SVR had been reached by 19/184 (10.3%) of patients with genotype 1, 54/138 (39.1%) with genotypes 2 or 3, and 4/29 (13.8%) of those with genotype 4. Within a total of 4466 patient-months follow-up (mean of 58 months), none of the 77 patients with SVR showed HCV-RNA rebounds, elevations in liver enzymes potentially linked to HCV, development of hepatocellular carcinoma or episodes of decompensated cirrhosis. In contrast, all 274 patients who did not reach SVR with HCV therapy showed evidence of persistent serum HCV RNA and 90% of them showed liver enzyme elevations during a total of 15344 patient-months follow-up (mean of 56 months). Moreover, 11 (4%) developed clinical complications of liver cirrhosis and two of them died of end-stage liver disease. CONCLUSIONS: HCV replication and HCV-related liver disease seem to be permanently halted in HIV/HCV-coinfected patients showing HCV-RNA clearance 6 months after completing any kind of IFN-based therapy. In contrast, complications of liver disease due to persistent HCV infection continue to occur in non-responders. The role of maintenance HCV therapy should be explored in HIV/HCV-coinfected patients.     

Impact of ribavirin exposure on early virological response to hepatitis C therapy in HIV-infected patients with chronic hepatitis C

BACKGROUND: The use of pegylated interferon (PEG-IFN) plus ribavirin (RBV) is currently the recommended treatment for chronic hepatitis C virus (HCV) infection. Coinfection with HIV is a negative predictor of response, for reasons not well understood. METHODS: We examined the virological response at weeks 4 and 12 in 198 HCV/HIV-coinfected patients enrolled in a prospective trial in which PEG-IFN alpha 2a (180 microg per week) and RBV (1000-1200 mg daily) were provided. RESULTS: In an on-treatment analysis, 52.8% of patients achieved undetectable HCV-RNA (<600 IU/ml) at week 4, while 63% and 77.2% of patients had a decline of at least 2 and 1 log10, respectively. At week 12, 73.1% of patients reached undetectable HCV-RNA, and 83.5% and 89% achieved at least a 2- and 1-log10 drop, respectively. More than 85% of HCV genotypes 2/3 cleared HCV-RNA at week 4, a proportion significantly higher when compared with genotypes 1 (33.8%) and 4 (28.6%). Multivariate logistic regression analysis identified genotype 3 and RBV exposure (mg/kg of body weight) as independent predictors of virological response at week 12 of therapy. CONCLUSION: Early virological response rates to PEG-IFN plus RBV in HCV/HIV-coinfected patients seem to be similar to those reported for HCV-monoinfected subjects. The use of suboptimal doses of RBV in most earlier trials might account for the low response rates seen in coinfected patients. To our knowledge, this is the first report demonstrating that RBV exerts a significant independent effect on early virological response. Therefore, strategies aimed at optimizing doses and adherence to RBV might help to improve responses to HCV therapy in coinfected patients.     

Impaired response to interferon-alpha2b plus ribavirin in cirrhotic patients with genotype 3a hepatitis C virus infection

Patients with chronic infection with the 3a genotype of hepatitis C virus (HCV) are considered as 'easy-to-treat' with interferon/ribavirin (IFN/RBV), independent of liver disease severity. However, patients with extensive fibrosis or cirrhosis were under-represented in all the registration Phase III trials performed so far. To assess the influence of liver fibrosis on the outcome of anti-HCV therapy, all patients with genotype 3a hepatitis C who were naive to IFN-based therapies, and received RBV combined with standard IFN or pegylated IFN-(alpha2b (peg-IFN-alpha2b) as standard of care for their disease, were investigated at our centre. A sustained virological response (SVR) was achieved in 68 of 91 patients (75%) independent of IFN type, pretreatment viraemia, clearance of HCV RNA at week 4 and relevant co-morbidities. A SVR was less common in cirrhotics (6 of 17) than in non-cirrhotics (62 of 74; 35% vs 84%; P<0.0005). Compared to non-cirrhotics, the age and sex adjusted odds ratio (OR) of treatment failure for cirrhotics was 10.1 (95% confidence interval: 2.4-41.7). By multivariate analysis, cirrhosis was the only predictor of non-SVR. In conclusion, cirrhosis is an independent predictor of IFN/RBV treatment failure in patients chronically infected with HCV 3a and is associated with an increased risk of post-treatment hepatitis relapse. Evaluation of liver fibrosis is important in the management of patients with genotype 3a hepatitis C, since it helps to predict response to IFN/RBV therapy.     

A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicentre study in Taiwan

BACKGROUND: The long-term benefit for chronic hepatitis C (CHC) patients treated with interferon (IFN)/ribavirin (RBV) combination therapy remains unclear. We aimed to evaluate the long-term effects of IFN monotherapy and IFN/RBV combination therapy on reducing hepatocellular carcinoma (HCC) and mortality in patients with chronic hepatitis C virus (HCV) infection, adjusting for risk factors. METHODS: A total of 1,619 patients with biopsy-proven CHC, including 1,057 receiving IFN-based therapy (760 on IFN/RBV combination therapy) and 562 untreated controls from three medical centres and one regional core hospital in Taiwan were enrolled in this retrospective-prospective cohort study. RESULTS: The incidence of HCC and survival during a follow-up period of 1.0-15.3 (mean 5.18) and 1-16 (mean 5.15) years in treated and untreated patients, respectively, was analysed using Cox proportional hazards regression. The cumulative incidence of HCC was 35.2% and 12.2% for untreated and treated groups, respectively (P=0.0013). The cumulative survival rate was 93.1% and 96.2% for untreated and treated groups, respectively (P=0.3928). Significantly lower incidences of HCC and mortality were observed in sustained virological responders (both for IFN monotherapy and IFN/RBV combination) but not in nonresponders when compared with untreated patients. HCV genotype 1 patients had significantly higher incidences of HCC than genotype non-1 patients. In multivariate analysis, pre-existing cirrhosis, non-response, HCV genotype-1 and age were associated with HCC; pre-existing cirrhosis and non-response correlated to mortality. CONCLUSION: A sustained virological response secondary to IFN monotherapy or IFN/RBV combination therapy could reduce the risk for HCC and improve survival of CHC patients.