Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based anti-viral therapy
01 Feb 2006-Alimentary Pharmacology & Therapeutics (Blackwell Science Ltd)-Vol. 23, Iss: 4, pp 507-511
TL;DR: This data indicates that combination anti‐viral therapy achieves a sustained virological response (defined as HCV‐RNA negativity 6 months after the end of therapy) of 56% of patients with chronic hepatitis C.
Abstract: Summary
Background Combination anti-viral therapy achieves a sustained virological response (defined as HCV-RNA negativity 6 months after the end of therapy) of 56% of patients with chronic hepatitis C. Little is known about long-term durability of HCV-RNA negativity in patient treated with pegylated interferon.
Aim To evaluate the durability of virologic response in patients with sustained virological response to anti-viral therapy treated at our centre.
Methods A total of 187 sustained virological responses (50% genotype 1, 42% genotype 2 or 3 and 8% genotype 4; 20% with cirrhosis) with a follow-up of >12 months post-therapy were studied. Twelve patients received monotherapy with interferon-alpha2a or −2b. One hundred and seventy-five received combination therapy with ribavirin and standard interferon-alpha (n = 73) or pegylated interferon-alpha2a or 2b (n = 102). Qualitative serum HCV-RNA was tested by COBAS AMPLICOR HCV test, v2.0.
Results Median follow-up time was 29 months (range 12–172). Recurrence of HCV infection was not observed in any of the 187 sustained virological responders. Alanine aminotransferase values were normal in 90% and two patients showed minimal elevation of alpha-fetoprotein levels.
Conclusions No recurrence of HCV infection was seen in any patient. Thus, long-term prognosis in chronic hepatitis C patients with a sustained virological response to therapy with pegylated interferon ± ribavirin is promising, but long-term studies need to continue.
Citations
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TL;DR: After initiation of treatment, initial viral decline with undetectable HCV-RNA at week 4 of therapy (RVR) is the best predictor of sustained virologic response independent of HCV genotype.
335 citations
Cites background from "Long-term follow-up of chronic hepa..."
...Moreover, the 5-year durability of an SVR was in excess of 99% in patients treated with pegylated (PEG) IFN [113–116]....
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TL;DR: In a large cohort of patients monitored for the durability of an SVR, the SVR was maintained for almost 4 years after treatment with peginterferon alfa-2a alone or in combination with ribavirin, and in patients with chronic hepatitis C infection, these patients should be considered as cured.
333 citations
TL;DR: Chronic HCV infection is curable with SVR attainment, and with cure comes improved liver histology and more favorable clinical outcomes, in comparison with patients who do not achieve the same therapeutic milestone.
Abstract: Sustained virologic response (SVR) is defined as aviremia 24 weeks after completion of antiviral therapy for chronichepatitisCvirus(HCV)infection.InanalysesofSVRdurability,theincidenceoflaterelapseisextremely low (,1%). Histologic regression of both necroinflammation and fibrosis has been demonstrated in paired liver biopsy samples in SVR-achieving patients. More noteworthy is the sustained responder’s favorable prognosis even with baseline cirrhosis; despite mostly retrospective analyses, relative to nonresponders or to those untreated, patients with SVR have significantly fewer liver-related complications, less hepatocellular carcinoma, and fewer liver-related deaths. Although HCV is associated with insulin resistance, successful eradication of HCV appears to reduce the risk of impaired fasting glucose and diabetes development. In summary, chronic HCV infection is curable with SVR attainment, and with cure comes improved liver histology and more favorable clinical outcomes, in comparison with patients who do not achieve the same therapeutic milestone.
271 citations
Additional excerpts
...…[21] PEG/RBV 231 0.9 50 IU/mL 38 (median) 32–42 Giannini et al 2010 [22] IFN, IFN/RBV, PEG/RBV 147 0.7 50 IU/mL 28 (mean) 4–124 Desmond et al 2006 [23] IFN, IFN/RBV, PEG/RBV 187 0 50 IU/mL 29 (median) 12–172 Formann et al 2006 [24] IFN, IFN-lymph, IFN-leuk 87 0 NR NR 36–76 Toccaceli et al 2003 [25]...
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...IFN, IFN/RBV, PEG/RBV 187 0 50 IU/mL 29 (median) 12–172 Formann et al 2006 [24]...
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TL;DR: The evidence supports the notion that risk of recurrence is driven by reinfection, and sustained virological response is durable in patients treated for hepatitis C virus.
Abstract: Infection with the hepatitis C virus (HCV) is a significant public health concern associated with a high burden of morbidity and mortality [1, 2]. Recent estimates suggest that worldwide, of the 185 million individuals infected, over 700 000 people die annually as a result of infection [3, 4].
The attainment of a sustained virological response (SVR), defined as aviremia 12 or 24 weeks after the completion of antiviral therapy (SVR12 or SVR24), is associated with an improved prognosis compared with patients either untreated or failing therapy. These benefits include improved histology, reduced risk of hepatocellular carcinoma, and improved overall survival [5, 6].
Despite these benefits, treatment uptake for chronic HCV has been low due to complexities of treatment and poor success rates. The availability of new highly efficacious regimens provides the foundation for marked treatment scale-up; however, high costs are currently limiting access [7–10].
One challenge to treatment scale-up is the risk of HCV recurrence, either as late relapse post-SVR or reinfection following treatment. HCV recurrence is a particular concern in patients with ongoing high-risk behaviors, such as injecting drug users (IDUs), who are more susceptible to reinfection, and also patients coinfected with human immunodeficiency virus (HIV) who may be at increased risk of relapse due to their immunocompromised status [11–15].
A number of studies have been carried out to examine the durability of treatment-induced SVR in patients with chronic HCV in a variety of patient populations. Our aim was to systematically review the existing evidence and undertake meta-analysis to provide summary estimates of the recurrence rate by risk group. The secondary aim was to evaluate the contribution of late relapse and of reinfection to the recurrence rate. This work fits within the theme one of the PROGRESS framework for prognosis research (“fundamental prognosis research”) and will provide a clearer understanding of HCV recurrence to inform the provision of antiviral therapy [16].
243 citations
TL;DR: This review gives a summary of available data regarding “occult” HCV infection despite constantly negative serum HCV RNA1-14.
94 citations
References
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TL;DR: In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferonAlfa- 2b plus Ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interfer on alfa -2b plus ribvirin or pegin terferonalfa-3a alone.
Abstract: Background Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Methods A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 μg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. Results A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) th...
6,523 citations
TL;DR: In patients with chronic hepatitis C, the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin, and this randomised trial found that the benefit is mostly achieved in patients with HCV genotype 1 infections.
6,228 citations
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TL;DR: Findings, i.e. that as-needed AO provided for a period of 3 months had no effect on quality of life and walked distance, are against the stream of current guidelines.
Abstract: I. Garcia-Talavera's reaction to the results of our trial of ambulatory oxygen (AO) in oxygen-dependent chronic obstructive pulmonary disease (COPD) is of no surprise to us. We realise that our findings, i.e. that as-needed AO provided for a period of 3 months had no effect on quality of life and walked distance 1, are against the stream of current guidelines ( i.e. that active patients receiving long-term oxygen therapy should have both stationary and mobile systems of oxygen delivery) 2 …
3,097 citations
TL;DR: Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype, and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribvirin was statistically inferior to low-dose Ribavirin.
Abstract: BACKGROUND:
Treatment with pegylated interferon (peginterferon) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. OBJECTIVE:
To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or standard dose of ribavirin. DESIGN:
Randomized, double-blind trial. SETTING:
99 international centers. PATIENTS: 1311 patients with chronic hepatitis C. PATIENTS:
1311 patients with chronic hepatitis C. INTERVENTION:
Peginterferon-?2a, 180 ?/wk, for 24 or 48 weeks plus a low-dose (800 mg/d) or standard weight-based dose (1000 or 1200 mg/d) of ribavirin. Measurement: Sustained virologic response: undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up. RESULTS:
Overall and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribavirin was statistically superior to low-dose ribavirin. In patients with HCV genotype 1, absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2% (95% CI, 3.6% to 18.9%) and 11.9% (CI, 4.7% to 18.9%), respectively, between standard- and low-dose ribavirin. Sustained virologic response rates for peginterferon-alpha2a and standard-dose ribavirin for 48 weeks were 63% (CI, 59% to 68%) overall and 52% (CI, 46% to 58%) in patients with HCV genotype 1. In patients with HCV genotypes 2 or 3, the sustained virologic response rates in the 4 treatment groups were not statistically significantly different. CONCLUSION:
Treatment with peginterferon-?2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.
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