Limited effectiveness and safety profile of protease inhibitor-based triple therapy against chronic hepatitis C in a real-world cohort with a high proportion of advanced liver disease

Maasoumy, Benjamin; Port, Kerstin; Deterding, Katja; Siederdissen, Christoph Höner zu; Markova, Antoaneta; Rogalska-Taranta, Magdalena; Manns, Michael P.; Wedemeyer, Heiner; Cornberg, Markus

doi:10.1097/meg.0000000000000121

Cited by 24 publications

(18 citation statements)

References 9 publications

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“…Other real-life cohort studies worldwide have confirmed the abovementioned results [12][13][14][15]. The efficacy of triple antiviral therapy in patients with advanced fibrosis or cirrhosis is higher than that of double antiviral therapy with P-R, but it is still far from being optimal.…”

Section: Telaprevir and Boceprevirsupporting

confidence: 65%

Sustained Virological Response and Hepatitis C-Related Cirrhosis: a World of Opportunities

Londoño

Hernández-Blanco

Díaz-González

2015

Curr Hepatology Rep

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Hepatitis C represents a serious health issue. Approximately 185 million people are infected with the virus and 350,000 people die every year as a consequence of this disease. New direct-acting antiviral agents achieve viral eradication in more that 90 % of the treated patients. More importantly, patients with advanced liver disease or those nonresponders to a previous course of treatment with an interferon-based therapy will also have the chance of curing hepatitis C (HCV) infection with these new drugs. In compensated cirrhosis, effective antiviral therapies may improve liver outcomes avoiding the development of clinical decompensation or hepatocellular carcinoma. However, information about the effectiveness and safety of antiviral drugs in patients with more advanced disease (Child-Pugh B or C) is scarce and it is still unclear whether viral eradication translates into an improvement of liver function or cirrhosis regression.

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Section: Telaprevir and Boceprevirsupporting

confidence: 65%

Sustained Virological Response and Hepatitis C-Related Cirrhosis: a World of Opportunities

Londoño

Hernández-Blanco

Díaz-González

2015

Curr Hepatology Rep

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“…A nearly significant trend was noted with serum albumin levels of 35 g/l or greater (OR = 1.86, p = 0.061). A recent ‘real-life' German study found similar associations for the HCV genotype, platelet count and serum albumin level, and also showed a higher risk of experiencing a treatment failure for patients with a Child-Pugh score above 5 (p < 0.05) [50]. The IL28B genotype was also identified as a predictor of SVR12, with a higher probability of response among patients with the IL28B CC genotype (OR = 3.54, p = 0.031).…”

Section: Viral Efficacy During Phase III Trials Of Triple Therapymentioning

confidence: 81%

Antiviral Therapy in Patients with Hepatitis C Virus-Induced Cirrhosis

Bailly

Pradat²,

Virlogeux³

et al. 2015

Dig Dis

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Background: Opportunities to treat infection with hepatitis C virus (HCV) are evolving rapidly. From the introduction of interferon (IFN)-α monotherapy in the early 1990s to the approval of telaprevir- and boceprevir-based triple therapies with pegylated (PEG)-IFN-α and ribavirin (RBV) in 2011, the chances of curing patients infected with HCV genotype 1 have improved dramatically to reach approximately 70%. Significant further improvements that may cure virtually all HCV patients with an all-oral, IFN-free regimen are becoming progressively available. Key Messages: Historically, a PEG-IFN/RBV combination therapy of patients with liver cirrhosis was associated with lower virological rates and a worse safety profile. The advent of the first protease inhibitor-based triple therapy was long expected, but the promise fell rapidly because of the numerous side effects and the requirement for intensive clinical management in cirrhotic patients. The newer direct-acting antivirals (DAAs) target the viral polymerase with either nucleos(t)ide analogues or nonnucleosidic inhibitors, the viral protease and the viral NS5A protein. Several clinical trials have now shown that a combination of sofosbuvir (nucleosidic polymerase inhibitor) with daclatasvir or ledipasvir (NS5A inhibitors), or sofosbuvir with simeprevir (protease inhibitor), or a combination of ABT-450 (protease inhibitor) with ritonavir (ABT-450/r), the nonnucleosidic polymerase inhibitor ABT-333 and the NS5A inhibitor ABT-267, can achieve a sustained virological response in up to 95% of naive patients or previously treated patients, even in those who failed prior treatment with first-generation protease inhibitors. The best treatment regimens enable the achievement of comparable results even in cirrhotics, while other regimens still require RBV or a longer treatment duration to achieve optimal results. This improved risk/benefit ratio justifies early access programs of IFN-free regimens for cirrhotic patients. The remaining difficult-to-treat patients are cirrhotics infected with HCV genotype 3 and those with decompensated cirrhosis, for whom novel DAA combinations should be evaluated in clinical trials. Conclusions: As new DAAs are becoming available in early access treatment programs, treatment strategy studies are being performed to optimize treatment regimens with respect to the choice of DAAs and treatment duration, based on viral genotypes, prior treatment response and the presence of liver cirrhosis. In the near future, this should allow: (i) a decrease in the complications of HCV-induced cirrhosis, (ii) liver transplantations to be performed in virally cured patients, and (iii) the rescue of patients in the worst clinical situation (decompensated cirrhosis and HCV recurrence on liver graft).

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“…Historically, SVR rates in genotype 1 patients treated with peginterferon/ribavirin dual therapy in actual clinical practice have been 15-25 % lower than reported in clinical trials [13,14]. As reported by Price et al and noted in other ''real-world'' cohorts evaluating boceprevir-and telaprevirbased regimens, overall SVR rates were 4-20 % lower than those reported in clinical trials [15][16][17][18]. The observed differences in SVR rates likely reflect the diverse HCVinfected population treated in ''real-world'' practice, many of whom would never meet stringent clinical trial screening criteria and would never qualify for clinical trial enrollment due to existing comorbidities, laboratory abnormalities, or social issues.…”

mentioning

confidence: 78%

Effectiveness Research in the Evolving HCV Landscape

Backus¹,

Belperio²

2014

Dig Dis Sci

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Limited effectiveness and safety profile of protease inhibitor-based triple therapy against chronic hepatitis C in a real-world cohort with a high proportion of advanced liver disease

Abstract: The effectiveness and safety of PI-based triple therapy can be limited in real-world cohorts including large numbers of patients with advanced liver disease. Future therapies can only overcome these limitations if interferon-free regimens are established.

Cited by 24 publications

References 9 publications

Sustained Virological Response and Hepatitis C-Related Cirrhosis: a World of Opportunities

Sustained Virological Response and Hepatitis C-Related Cirrhosis: a World of Opportunities

Antiviral Therapy in Patients with Hepatitis C Virus-Induced Cirrhosis

Effectiveness Research in the Evolving HCV Landscape

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