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1.
INTRODUCTION Chronic hepatitis C viral (HCV) infection is well recognized as a major cause of cirrhosis and hepatocellular carcinoma. Spontaneous remission of the disease seems to be rare. After alfa-interferon was used as therapy for HCV infection in 1986[1], Interferon associated with Ribavirin became the standard treatment for this disease. Sustained virological response, def ined as HCV RNA PCR negative at 6 mo after the end of treatment (SVR-6), is considered to be a useful p…  相似文献   

2.
BACKGROUND: Treatment of acute hepatitis C (HCV) in HIV-infected patients has been poorly addressed. OBJECTIVE: To evaluate the efficacy and tolerability of a 24 week course of pegylated interferon alfa 2a (PegIFNalpha2a) and ribavirin for the treatment of acute HCV infection in HIV-infected patients. METHODS: This was a prospective pilot study of 25 consecutive HIV-infected men with acute HCV infection defined by documented HCV seroconversion to anti-HCV positive antibody and positive qualitative HCV RNA measurement. Patients with detectable HCV RNA (> 50 IU/ml) 12 weeks after diagnosis were offered treatment with PegIFNalpha2a (180 microg/week) and ribavirin (800 mg/day) for 24 weeks. Sustained virological response was defined by a negative qualitative HCV RNA measurement 24 weeks after the end of treatment. RESULTS: At baseline, 23 patients were taking HAART, 23 patients had HIV RNA < 200 copies/ml and a median CD4 count of 345 cells/microl. Only one patient, with genotype 3 HCV, had a spontaneous clearance of HCV RNA. Of the remaining 24 patients, four refused anti-HCV therapy, ribavirin was contraindicated in one and 19 initiated anti-HCV therapy. Median time between acute HCV diagnosis and initiation of study treatment was 14 weeks. Of the 14 patients who have achieved the post-treatment follow-up at 24 weeks, 10 had a sustained virological response (71%). Study treatment was well tolerated, with no change in CD4 cell count. CONCLUSION: Early treatment of acute HCV infection with PegIFNalpha2a and ribavirin for 24 weeks yields a high sustained virological response rate in HIV-infected patients.  相似文献   

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

4.
OBJECTIVE: An early virological response has been shown to be predictive of a sustained virological response to antiviral treatment in chronic hepatitis C infection. The aim of the study was to analyse viral kinetics during the first 6 weeks of treatment (interferon plus ribavirin) in 18 relapsed hepatitis C patients after a first course of interferon monotherapy. METHODS: We studied 18 relapsed patients treated with interferon and ribavirin. A sustained virological response (negative HCV RNA measured by polymerase chain reaction 6 months after the end of therapy) was obtained in 12 patients. Samples were obtained before therapy and each week for 6 weeks during therapy; HCV RNA levels were determined using quantitative bDNA. RESULTS: At the end of week two, a viral-load drop of more than 2.20 log was observed in all the 12 patients with a sustained virological response and in none of the six other patients. When we considered the median of the viral load reduction from baseline for each week of treatment, week two appeared to be the time point most predictive of a sustained viral response (positive predictive value 83%; negative predictive value 92%). CONCLUSION: During treatment with interferon plus ribavirin in relapsed hepatitis C patients, viral kinetics showed that the second week of treatment appeared to be the time point most predictive of a sustained viral response.  相似文献   

5.
Because interferon therapy exhibits low efficacy for cirrhotic patients infected with hepatitis C virus, this prospective study was conducted to determine effective interferon regimens tailored to treatment response by monitoring HCV RNA status. A total of 157 cirrhotic patients were enrolled to receive 9 million units (MU) of interferon three times a week. The HCV RNA values were drawn 8 weeks apart and the patients were randomized to a further 16 or 32 weeks of treatment after two sequential findings of negativity for HCV RNA. A total of 73 out of 157 patients (46%) proceeded to randomization to different durations of treatment, 37 short-course and 36 long-course (duration: 38 +/- 8 and 49 +/- 13 weeks; total amount of interferon: 940 +/- 240 and 1130 +/- 390 MU, respectively). The remaining 84 patients without two sequential negative serum HCV RNA determinations received 44.8 +/- 27.4 weeks of interferon (IFN) therapy with total amount of 993 +/- 633 MU. Of these 157 patients, sustained virological and biochemical response was shown in 32 (20%) and 37 patients (24%), respectively. Sustained virological and biochemical response rate in the randomized patients was significantly higher than in nonrandomized patients (41% vs. 2%, and 38% vs. 11%; each P <.01). Of the 73 randomized patients, the rate of sustained virological response in patients with long-course treatment (50%) was significantly higher than that of patients with short-course treatment (32%) (P =.026: log-rank test), and in patients with early disappearance of HCV RNA especially within 8 weeks, in patients with low virus load (相似文献   

6.
Background and objectivesEvidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma.MethodsA cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy.ResultsThe mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55%) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3%) vs. 8 (17%) responders and non responders respectively (p = 0.02).ConclusionPatients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.  相似文献   

7.
BACKGROUND AND AIMS: A proportion of liver transplanted patients with recurrent chronic hepatitis have a sustained virological response to combination therapy with interferon plus ribavirin. However, the long term benefit of antiviral therapy with regard to hepatitis C virus (HCV) RNA clearance remains unknown in patients with HCV recurrence. This study examined the long term biochemical, virological, and histological outcome in transplanted patients with recurrent chronic hepatitis who had a sustained virological response to antiviral therapy. PATIENTS AND METHODS: Fifty four patients with recurrent hepatitis C were treated with antiviral therapy involving induction by combination therapy (interferon (IFN) plus ribavirin) for six months and maintenance ribavirin therapy for 12 months. Fourteen patients who had recurrent chronic hepatitis and sustained virological response to antiviral therapy were followed for three years after the end of antiviral therapy. Serum alanine aminotransferases were assessed every three months during the observation period. Serum hepatitis C RNA detected by polymerase chain reaction was evaluated every six months during follow up, and protocol biopsy procedures were performed routinely every year. Semiquantitative histopathological assessment of allograft hepatitis was performed using the Knodell score and HCV was also detected by polymerase chain reaction on frozen graft tissue samples. RESULTS: At the end of antiviral therapy, the sustained response rate was 26%. A complete response (normal serum alanine aminotransferase level and undetectable serum HCV RNA) was achieved in 13/14 (93%) patients three years after the end of treatment. A comparison of liver histology findings before and after a mean of three years after antiviral therapy showed a clear improvement in 12/14 (86%) patients. In 5/14 (36%) patients, the last biopsy showed normal or near normal histological findings. After three years of follow up, the total Knodell score was 3.2 (range 1-8) versus 8.3 (range 5-12) before treatment (p=0.001). Graft HCV RNA was detectable before treatment in all 14 patients and was undetectable at the end of follow up in 13/14 (93%) patients tested. CONCLUSION: In patients with biochemical and virological responses induced by ribavirin and interferon, a complete response was sustained in 93% for at least three years after cessation of therapy. This long term response was associated with absence of detectable intrahepatic hepatitis C RNA and marked histological improvement.  相似文献   

8.
BACKGROUND/AIMS: HCV infection recurs almost in all HCV-positive patients receiving liver transplantation and carries a poor prognosis. Aim of this study was to analyze efficacy and effect on survival of antiviral therapy in this clinical setting. METHODS: Pegylated-interferon alpha-2b and ribavirin were administered at a dose of 1 microg/kg of bwt weekly and 600-800 mg/day. Planned duration of treatment was 24 or 48 weeks according to HCV genotype. Patients who failed to respond at week 24 were considered as non-responders. RESULTS: 61 patients were enrolled. According to intention-to-treat analysis, 44 (72%) patients were considered as treatment failure (31 non-responders, 4 relapsers, 9 dropout). Sustained virological response was achieved in 17 cases (28%). Genotype 2, higher doses of antivirals and absence of histological cirrhosis were predictors of sustained virological response. In the follow up, patients with sustained virological response had a significantly lower mortality compared to patients with treatment failure (chi2=6.9; P<0.01). CONCLUSIONS: Response rate to antiviral therapy in HCV reinfection after liver transplantation is higher if a full dose of antiviral drugs is administered and if treatment starts before histological cirrhosis has developed. Sustained virological response improves patient survival.  相似文献   

9.
BACKGROUND/AIMS: A combination of interferon alpha and ribavirin has been suggested to reach a higher rate of sustained virological response in patients with chronic hepatitis C than monotherapy. In this study we assessed the long-term efficacy of this combination therapy in the treatment of selected Italian naive chronic hepatitis C patients compared to interferon alpha monotherapy. METHODS: We enrolled 428 naive patients who were randomly assigned to receive either recombinant interferon alpha-2b and ribavirin for 24 weeks or interferon alpha-2b alone for 48 weeks. The primary end-point of the study was the rate of sustained virological response. Serum HCV RNA levels were determined before treatment; during treatment at weeks 12 and 24 in the patients receiving the combination therapy; at weeks 12, 24, 36 and 48 in the patients receiving monotherapy; and after therapy at weeks 12, 24 and 48 in the patients in both study groups. RESULTS: Sustained virological response was observed in 43% of the patients treated with combination therapy and in 14% of the patients treated with monotherapy. Logistic regression analysis showed that sustained response was associated with the combination therapy, with HCV genotype other than 1b, with an HCV viral load of 3x10(6) copies/ml or less, with an inflammation score of 7 or less, and with an estimated duration of disease of 10 years or less. CONCLUSIONS: A 24-week treatment course with interferon alpha-2b and ribavirin offers a greater chance of sustained virological response compared to treatment with interferon alpha-2b alone for 48 weeks, and may be indicated as initial therapy in such patients.  相似文献   

10.
Chronic infection with hepatitis C virus (HCV) may result in cirrhosis, liver failure, and hepatocellular carcinoma. A minority of patients have a sustained response to antiviral therapy, and nonresponders remain at risk of developing progressive liver disease. We conducted a randomized, controlled trial of therapy with the combination of interferon (IFN) and ribavirin in patients with chronic hepatitis C who had not responded to an initial course of therapy with IFN alone. A total of 124 patients were randomized to receive the combination of IFN and ribavirin for either 24 or 48 weeks and followed for an additional 24 weeks after stopping therapy. Thirty-eight treated patients (30.6%) achieved a sustained virologic response (undetectable HCV RNA at the 24-week follow-up point). This was associated with significant improvement in necroinflammatory activity noted on liver biopsy. Interestingly, there was not a statistically significant difference in response rates based on the duration of treatment; HCV genotype was the strongest predictor of a sustained response. Sustained responses were noted even in patients with poor predictive factors, including those with advanced hepatic fibrosis or cirrhosis, high levels of HCV RNA in serum, and those infected with HCV genotype 1. The study included 24 patients with normal serum alanine transaminase (ALT) values before therapy who had similar responses to those with initially elevated transaminase values. This study suggests that the combination of IFN and ribavirin is a useful modality of therapy in patients with chronic hepatitis C who did not respond to IFN alone.  相似文献   

11.
Background/Aims: We compared the efficacy and safety of the combined therapy of daily interferon α-2b and ribavirin with those of interferon α-2b three times per week alone or in combination with ribavirin in non-responder patients with hepatitis C virus (HCV) infection.Methods: A total of 376 patients were randomly assigned to receive interferon α-2b (6 MU three times per week for 24 weeks followed by 3 MU three times per week for 24 weeks) alone (group A) or in combination with ribavirin for 48 weeks (group B), or daily interferon α-2b (3 MU per day for 24 weeks followed by 3 MU three times per week for 24 weeks) and ribavirin (group C).Results: After 24 weeks of therapy, HCV RNA was undetectable in 11.7, 24.0, and 37.8% for groups A, B, and C, respectively. Sustained virological response was more frequent in patients who received combination therapy with three times weekly interferon (20.9%) or daily interferon (26.0%) than in patients who received interferon alone (5.8%) (P<0.001). The predictive HCV parameters for sustained response were a low viral load on day 7 and a negative HCV RNA on week 12.Conclusions: In conclusion, in non-responder patients with chronic hepatitis C, virological response with daily interferon and ribavirin, compared to interferon monotherapy, was significantly improved during treatment, although sustained virological response was similar for both combination therapies with ribavirin and three times a week or daily interferon.  相似文献   

12.
BACKGROUND/AIMS: Assessment of chronic hepatitis C outcome in sustained responders to interferon requires prolonged observation and close monitoring. We prospectively studied the impact of sustained response on histology and clinically relevant outcomes. METHODS: The 47 sustained responders (ten with cirrhosis) from two interferon trials involving 235 chronic hepatitis C patients (81 with cirrhosis) were included. Hepatitis C virus (HCV) RNA was assessed every 6 months, liver histological changes from baseline, 6-12 and 48-72 months after treatment discontinuation. RESULTS: The mean follow-up was 102 +/- 19 months. HCV RNA became undetectable in 36/47 responders. Four responders, who had remained viremic, later relapsed. The histology progressively improved in non-viremic and viremic patients, with a more marked improvement in the former (P = 0.0089), normalizing in 53 vs. 0% (P = 0.0220). No patient progressed to cirrhosis. One non-viremic cirrhotic patient developed a hepatocellular carcinoma. Non-responders from the two original trials had worse histological outcomes and those with cirrhosis had a higher rate of clinically relevant events compared with cirrhotics showing a sustained biochemical response (4.5 vs. 1.2 cases/100 person-years; CI for the difference, 0.3-6.3). CONCLUSIONS: Most sustained, virological responders without cirrhosis normalize liver histology in the long-term and are cured of the disease. Sustained responders remaining viremic still show histological improvement, albeit to a lesser extent.  相似文献   

13.

Context:

Attaining a sustained virological response with antiviral therapy is a sign of clinical cure for chronic hepatitis C patients. The aim of this meta-analysis was to evaluate the long-term efficiency and outcome of antiviral therapy in patients with hepatitis C who attained a sustained virological response.

Evidence Acquisition:

A literature search was performed on published articles between January 2008 and February 2014. Patients with Hepatitis C who received interferon with or without ribavirin therapy were enrolled. Relative risks were estimated using either fixed or random effect models.

Results:

Patients who attained sustained virological response had a less risk (85%) for all-cause mortality and about 63% reduced risk of hepatocellular carcinoma incidence than those who did not achieve sustained virological response. Based on deeply analysis, the stage of liver fibrosis was a risk factor at baseline for the incidence of hepatocellular carcinoma.

Conclusions:

Sustained virological response can reduce all-cause mortality and the incidence of hepatocellular carcinoma of patients with hepatitis C. Advanced liver fibrosis is still a risk factor for the incidence of hepatocellular carcinoma, in spite of hepatitis C patients attained a sustained virological response.  相似文献   

14.
To determine the effects of hepatitis G virus(HGV) infection on chronic hepatitis C virus infection(HCV) and to evaluate HGV response to interferon, weinvestigated HGV RNA by polymerase chain reaction in 247 Japanese patients with chronic HCVinfection (166 men and 81 women; 124 had chronichepatitis and 26 cirrhosis, and 97 hepatocellularcarcinoma). HGV RNA was detectable in 22 (8.9%)patients, among whom 21 were men: this male predominance wasstatistically significant (P < 0.01). There were nodifferences in age, aminotransferase level, stage ofliver disease, HCV RNA level by competitive polymerase chain reaction, genotype, or interferonresponse to HCV RNA between patients with HCV infectionalone or with HCV/HGV coinfection. Sustained eliminationof HGV RNA was found in 28.6% of the 14 treated patients with HCV/HGV coinfection. In the 14 treatedpatients, sustained elimination of both viruses was seenin two, HCV alone was eliminated in two, and HGV alonewas eliminated in two. Aminotransferase level improvement by interferon treatment wasassociated with clearance of HCV, but not of HGV. Thus,HGV infection had no apparent effects on HCV infection,and the sensitivity of HGV to interferon is comparable to but independent of HCV.  相似文献   

15.
16.
BACKGROUND: The key end point for treatment efficacy in chronic hepatitis C is absence of detectable virus at six months after treatment. However, the incidence of clinical events during long term follow up of patients with sustained virological response is still poorly documented and may differ between the Eastern and Western world. AIMS: To assess clinical end points during long term follow up of European patients with a sustained virological response to interferon monotherapy. METHODS: Meta-analysis of individual patient data from eight European protocolled follow up studies of interferon treatment for chronic hepatitis C. RESULTS: A total of 286 sustained virological responders and 50 biochemical responders (detectable virus but normal alanine aminotransferase levels) were followed up for 59 months. Fifteen sustained virological responders (5.2%) had cirrhosis before treatment and 112 (39%) had genotype 1. The late virological relapse rate after five years of follow up was 4.7% (95% confidence interval (CI) 2.0-7.4) among sustained virological responders; all late relapses occurred within four years after treatment. Among sustained virological responders, the rate of decompensation after five years of follow up was 1.0% (95% CI 0.0-2.3) and none developed hepatocellular carcinoma (HCC). Survival was comparable with the general population, matched for age and sex, the standard mortality ratio being 1.4 (95% CI 0.3-2.5). Clinical outcome of patients with cirrhosis was similar to other sustained virological responders. For biochemical responders, the rates of development of decompensation and HCC during long term follow up were 9.1% (95% CI 0.5-17.7) and 7.1% (95% CI 0-15.0), respectively. CONCLUSIONS: Five year survival of European sustained virological responders was similar to the overall population, matched for age and sex. No HCCs were detected during long term follow up.  相似文献   

17.
Aim:  A nationwide survey in Japan revealed that nearly one-fifth of human immunodeficiency virus (HIV)-positive patients are co-infected with hepatitis C virus (HCV). We conducted a study to further analyze the features of liver disease in HIV–HCV co-infected patients.
Methods:  We analyzed 297 patients from eight hospitals belonging to the HIV/AIDS Network of Japan.
Results:  HCV genotypes 1, 2, 3, 4 and mixed genotypes were detected in 55.2, 13.7, 18.9, 0.9 and 11.3% of patients, respectively, in contrast to the fact that only genotypes 1 and 2 are detected in HCV mono-infected patients in Japan. This is compatible with the transmission of HCV through imported blood products contaminated by HCV. Sixteen of 297 HIV–HCV co-infected patients had advanced liver disease accompanied by ascites, hepatic encephalopathy or hepatocellular carcinoma. The average age of such patients was 41.1 ± 14.0 years, which was much younger than that of HCV mono-infected patients with the same complications. The progression speed of liver disease estimated from the changes in the levels of serum albumin, bilirubin, or platelet was slower in patients who achieved sustained virological response with interferon treatment than in those who did not receive it. The overall sustained virological response rate to interferon treatment was 43.3%.
Conclusions:  Our findings suggest that liver disease is more advanced in HIV–HCV co-infected patients than in HCV mono-infected patients, and interferon treatment may retard the progression of liver disease in such patients.  相似文献   

18.
BACKGROUND: The role combination therapy with interferon alfa-2b and tribavirin (US: ribavirin) plays in producing sustained virological responses in patients with HIV and chronic hepatitis C (HCV) infection is still unknown. OBJECTIVES: To determine the feasibility and sustained response of interferon alfa-2b and tribavirin combination therapy. DESIGN: Phase II study. METHODS: Seventeen patients were enrolled at the National Cancer Institute, Aviano, Italy and received combination therapy with interferon alfa-2b 3 MIU subcutaneously three times a week plus tribavirin 1000-1200 mg/day for 24 weeks. Antiretroviral therapy was concomitantly given in all but one patient. RESULTS: At the end of treatment, five (31%) patients achieved clearance of HCV RNA and 11 (69%) showed normalized liver function enzyme levels. In three patients, serum HCV RNA concentration was still undetectable 24 weeks after treatment, with an overall sustained virological response rate of 19% The serum liver enzymes were still normal in 10 patients 24 weeks after treatment, the overall sustained biochemical response rate being 62% All patients with HCV RNA clearance at the end of treatment and 24 weeks after treatment had a concomitant biochemical response. Overall the combination treatment was well tolerated. CONCLUSIONS: Our data confirm that the combination of interferon alfa-2b and tribavirin is well tolerated and feasible in patients with HIV-HCV co-infection and it can be associated safely with highly active antiretroviral therapy. The sustained response achieved with the drug combination does not seem to be any better than that achieved with 12 months of monotherapy with interferon alfa-2b.  相似文献   

19.
We investigated the efficacy of ribavirin plus interferon (IFN) α on GB virus-C (GBV-C)/hepatitis G virus (HGV) viraemia and compared it with that of interferon α alone in patients coinfected with hepatitis C virus (HCV) and GBV-C/HGV. Serum HCV and GBV-C/HGV-RNA were studied in eight patients with HCV and GBV-C/HGV coinfection, five received IFNα and three received oral ribavirin plus IFNα. Mean serum GBV-C/HGV titre at the end of therapy was significantly lower than the titre just before therapy and patients with lower pretreatment titre had a better sustained response rate. Sustained virological response of GBV-C/HGV to IFNα alone and ribavirin plus IFNα at the end of follow up was observed in one each, respectively. Thus, GBV-C/HGV in patients with HCV and GBV-C/HGV coinfection does respond to IFNα and ribavirin plus IFNα may not induce a higher sustained response.  相似文献   

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