Retreatment of Patients who Failed Daa-Combination Therapies: Real-World Experience from a Large Hepatitis C Resistance Database

Vermehren, Johannes; Susser, S.; Dietz, Julia; Hahn, Thomas von; Petersen, J.; Hinrichsen, Holger; Spengler, Ulrich; Mauss, S; Berg, CP; Zeuzem, Stefan; Sarrazin, C.

doi:10.1016/s0168-8278(16)00128-8

Cited by 35 publications

(36 citation statements)

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“…Furthermore, the presence of specific NS5A RAVs before a first‐ and, even more, a second‐line NS5A‐including regimen can significantly affect the achievement of a SVR in cirrhotic patients . At present, however, few real‐life data are available on DAA failures, and an exhaustive description of clinical characteristics of failing patients, along with their resistance profile, is still largely missing …”

Section: Introductionmentioning

confidence: 99%

Multiclass HCV resistance to direct‐acting antiviral failure in real‐life patients advocates for tailored second‐line therapies

Maio¹,

Cento²,

Lenci³

et al. 2017

Liver International

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Section: Introductionmentioning

confidence: 99%

Multiclass HCV resistance to direct‐acting antiviral failure in real‐life patients advocates for tailored second‐line therapies

Maio¹,

Cento²,

Lenci³

et al. 2017

Liver International

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“…Fortunately for these patients, excellent SVR rates with combination regimens including second generation DAAs have already been presented [2]. The nearby future is even looking bright for those few patients who failed to attain SVR with the currently available IFN-free regimens [3]. Although larger studies are needed, various combinations of pangenotypic and potent DAAs of various classes appear to result in SVR in almost all these patients [4,5].…”

Section: Introductionmentioning

confidence: 99%

Reversion of disease manifestations after HCV eradication

Meer

Berenguer

2016

Journal of Hepatology

161

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Chronic infection with the hepatitis C virus (HCV) may lead to hepatic fibrosis and eventually cirrhosis, at which stage, patients have a substantial risk of liver failure, hepatocellular carcinoma (HCC) and liver-related death. Moreover, HCV infection is associated with several extrahepatic manifestations which impact the quality of life and increase the non-liver-related mortality rate. For patients with compensated liver disease, interferon (IFN)-based antiviral therapy has been a treatment option for over two decades. Long-term follow-up studies indicated that among those with sustained virological response (SVR) the extend of hepatic fibrosis can regress and that their risk of cirrhosis-related complications (including HCC) is reduced, also in case of cirrhosis. Recent population-based studies extended these observations for solid extrahepatic outcomes, such as end-stage renal failure and cardiovascular events. Most importantly, SVR has been associated with prolonged overall survival. These results highlight the importance of the development of new direct-acting antivirals (DAAs), by which almost all patients are able to eradicate HCV in a comfortable manner. Based on the excellent first experiences with the DAAs, physicians gained confidence to use these drugs among patients with decompensated cirrhosis on a more regular basis as well. This was not possible with interferon therapy. Also in this high risk population the DAAs show high SVR rates with improvements in biochemical parameters of liver function shortly after therapy, especially in case of SVR. In fact, some patients could actually be removed from the liver transplantation waiting list due to clinical improvement following DAA therapy. How these short-term results translate into a prolonged (long-term) survival has yet to be determined, as well as which patients with decompensated liver disease are likely or not to benefit from viral eradication. Here we review the current data regarding the beneficial clinical outcome with antiviral therapy as well the remaining uncertainties in this field, both for patients with compensated liver disease and patients with decompensated liver disease.

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“…NS5A RAVs can be found in the majority of treatment failures and these RAVs may persist for several years thereafter, thereby limiting re-treatment options [85,86]. While the presence of baseline RAVs may not have a significant influence on overall SVR chances to a first course of DAA therapy, few data exist on their impact on re-treatment in patients who failed a DAA treatment [87,88]. Thus, failure to DAAs should be avoided by choosing the best regimen and treatment duration available for each individual patient, particularly in the presence of additional negative response predictors such as cirrhosis and prior failure to PegIFN-based therapy.…”

Section: ) Limiting the Risk Of Drug-drug-interactionsmentioning

confidence: 99%

Diagnostics in hepatitis C: The end of response-guided therapy?

Maasoumy

Vermehren

2016

Journal of Hepatology

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On-treatment hepatitis C virus (HCV) RNA has been used to predict response to interferon (IFN)-based therapy. The concept of response-guided treatment (RGT) was established to determine optimal treatment duration and to early identify patients not responding to futile therapies. RGT helped to improve sustained virologic response (SVR) rates and lower the rates of adverse effects. RGT was of particular importance for telaprevir- and boceprevir-based triple therapies. RGT strategies are dependent on highly sensitive and reproducible HCV RNA quantification. However, different HCV RNA assays are used in routine clinical practice and these differ significantly in their performance characteristics. The development of IFN-free therapies has fundamentally changed the role of on-treatment HCV RNA for SVR prediction. Given the high efficacy and excellent tolerability of IFN-free regimens, the interest in treatment individualization has decreased. However, shorter treatment durations may still be desirable, particularly with respect to the high costs of current IFN-free direct-acting antiviral agents (DAAs). Moreover, some difficult-to-treat patients remain, e.g., those infected with HCV genotype 3 in whom the current standard of care may not always be sufficient to achieve SVR, especially in treatment-experienced patients with cirrhosis. Here, a RGT extension may be feasible. However, current data on the predictive value of on-treatment HCV RNA are limited and have shown conflicting results. As more potent DAAs become available, the role of response prediction may diminish further. Currently, shorter treatment duration is only based on baseline HCV RNA whereas no RGT strategy is recommended for any of the approved DAA regimens available.

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Retreatment of Patients who Failed Daa-Combination Therapies: Real-World Experience from a Large Hepatitis C Resistance Database

Cited by 35 publications

References 0 publications

Multiclass HCV resistance to direct‐acting antiviral failure in real‐life patients advocates for tailored second‐line therapies

Multiclass HCV resistance to direct‐acting antiviral failure in real‐life patients advocates for tailored second‐line therapies

Reversion of disease manifestations after HCV eradication

Diagnostics in hepatitis C: The end of response-guided therapy?

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