HCV targeting of patients with cirrhosis

Ferenci, Péter; Kozbial, K; Mandorfer, Mattias; Hofer, Harald

doi:10.1016/j.jhep.2015.06.003

Cited by 53 publications

(50 citation statements)

References 77 publications

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“…The remaining patients were treated for 16 to 24 weeks and all patients achieved SVR. However, this was not a randomized study and data have not yet been fully published [107]. In our own study, detectable/<12 IU/ml HCV RNA was frequently seen with the ART assay even at the end of therapy.…”

Section: Hcv Rna Quantification For the Prediction Of Svr During Simementioning

confidence: 71%

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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Section: Hcv Rna Quantification For the Prediction Of Svr During Simementioning

confidence: 71%

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

Maasoumy

Vermehren

2016

Journal of Hepatology

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“…Prospective, randomized studies investigating (PEG-)IFN-free treatment which enrolled a significant number of patients with decompensated cirrhosis (Child-Pugh (CP) score > 8; MELD score > 16) are scarce, and safety as well as efficacy data are only available in individual cases for patients with a MELD score > 22 (table 2) [38,39,40,41,42,43,44,45]. In the ALLY-1 study, which enrolled patients with advanced cirrhosis and patients after liver transplantation, sustained virologic response (SVR) was achieved in 11/12 (92%), 30/32 (94%), and 9/16 (56%) patients with CP class A, B, and C cirrhosis, respectively [42].…”

Section: Antiviral Therapy In Hcv-associated Liver Cirrhosis and Hcv mentioning

confidence: 99%

“…In the ALLY-1 study, which enrolled patients with advanced cirrhosis and patients after liver transplantation, sustained virologic response (SVR) was achieved in 11/12 (92%), 30/32 (94%), and 9/16 (56%) patients with CP class A, B, and C cirrhosis, respectively [42]. The chance of achieving SVR seems therefore inversely correlated with liver function in patients with advanced cirrhosis prior to liver transplantation, although data are inconsistent in different studies [38,39,40,41,42,43]. Reliable predictive markers to estimate SVR or the clinical course during and after IFN-free therapy have not yet been identified in patients with decompensated HCV-associated cirrhosis.…”

Section: Antiviral Therapy In Hcv-associated Liver Cirrhosis and Hcv mentioning

confidence: 99%

“…Recently, a safety warning by the FDA resulted in a contraindication for DSV in combination with OMV and PTV/r in patients with liver cirrhosis CP ≥ B [52]. Therefore, only SOF plus RBV, and DCV/SOF as well as LDV/SOF alone or in combination with RBV are approved treatment options in patients with decompensated cirrhosis, while comprehensive safety data of SMV in patients with decompensated cirrhosis are still pending [38,39,40,41]. …”

Section: Antiviral Therapy In Hcv-associated Liver Cirrhosis and Hcv mentioning

confidence: 99%

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Pre- and Post-Transplant Antiviral Therapy (HBV, HCV)

Welker

Zeuzem

2016

Visc Med

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Background: Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-associated liver cirrhosis is a major indication for liver transplantation. This concise review gives an overview about current interferon (IFN)-free treatment options before and after liver transplantation in HBV- or HCV-associated liver disease. Methods: A PubMed database search using the terms hepatitis B, hepatitis C, cirrhosis, and liver transplantation was performed to identify significant clinical studies as well as national and international guidelines. Results: Studies investigating IFN-free treatment in patients with decompensated HBV as well as in HCV-associated cirrhosis are scarce. Hepatic recompensation during antiviral therapy seems more frequent in patients with HBV than in those with HCV-associated cirrhosis. Graft hepatitis B or C is characterized by an accelerated and unfavorable course. Graft infection prophylaxis is safe and efficacious in HBV-related liver transplantation. Eradication of HCV prior to liver transplantation prevents HCV graft infection, and IFN-free treatment of established HCV graft infection is safe and associated with high sustained virologic response rates. Conclusion: Patients with HBV-associated cirrhosis should be treated prior to liver transplantation, and receive a continuing graft infection prophylaxis thereafter. Patients with HCV-associated decompensated cirrhosis may be considered as candidates for antiviral therapy prior to liver transplantation or may be treated subsequently.

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“…Although some studies investigated patients with “decompensated” cirrhosis, data are scarce in patients with a MELD score higher than 15[69]. From the limited data may be concluded that patients with CPT class C cirrhosis have lower SVR 12 rates than patients without or with compensated cirrhosis.…”

Section: Approved Daa-based Treatment In Patients With Decompensated mentioning

confidence: 99%

Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection

Weiler¹,

Zeuzem²,

Welker³

2016

WJG

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Chronic hepatitis C is a major reason for development of cirrhosis and hepatocellular carcinoma and a leading cause for liver transplantation. The development of direct-acting antiviral agents lead to (pegylated) interferon-alfa free antiviral therapy regimens with a remarkable increase in sustained virologic response (SVR) rates and opened therapeutic options for patients with advanced cirrhosis and liver graft recipients. This concise review gives an overview about most current prospective trials and cohort analyses for treatment of patients with liver cirrhosis and liver graft recipients. In patients with compensated cirrhosis Child-Pugh-Turcotte (CTP) class A, all approved agents are safe and SVR rates do not significantly differ from patients without cirrhosis in general. In patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir, velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be achieved. Especially for patients with a model of end stage liver disease score higher than 15 and therefore eligible for liver transplantation, data is scarce. Reported SVR rates in patients with cirrhosis CTP class C are lower compared to patients with a less severe liver disease. In liver transplant recipients with a maximum of CTP class A, SVR rates are comparable to patients without LT. Patients with decompensated graft cirrhosis should be treated on an individual basis.

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HCV targeting of patients with cirrhosis

Cited by 53 publications

References 77 publications

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

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

Pre- and Post-Transplant Antiviral Therapy (HBV, HCV)

Concise review: Interferon-free treatment of hepatitis C virus-associated cirrhosis and liver graft infection

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