Real World Experience of Chronic Hepatitis C Retreatment with Genotype Specific Regimens in Nonresponders to Previous Interferon-Free Therapy

Zarębska-Michaluk, Dorota; Buczyńska, Iwona; Simon, Krzysztof; Tudrujek-Zdunek, Magdalena; Janczewska, Ewa; Dybowska, Dorota; Sitko, Marek; Dobracka, Beata; Jaroszewicz, Jerzy; Pabjan, Paweł; Klapaczyński, Jakub; Laurans, Łukasz; Mazur, Włodzimierz; Socha, Łukasz; Tronina, Olga; Parczewski, Miłosz; Flisiak, Robert

doi:10.1155/2019/4029541

Cited by 15 publications

(18 citation statements)

References 34 publications

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“…In addition, the general tendency before approval of VOX/VEL/SOF was to re-treat patients only with high urgency caused by advanced liver disease [26]. In line with the observation from other cohorts [27,28], patients in the present study who received rescue therapy in comparison to patients who did not receive re-treatment more often had liver cirrhosis (52.6 % versus 42.9 %, respectively).…”

Section: Discussionsupporting

confidence: 84%

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy – data from the German hepatitis C registry (DHC-R)

et al. 2020

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Background Virologic failure to approved combinations of direct antiviral agents (DAA) in patients with chronic hepatitis C virus (HCV) infection is rare. Mostly it involves difficult to treat patients with advanced liver disease and prior interferon-experience. Before approval of VOX/VEL/SOF, a restricted number of patients received rescue treatment, and the choice of DAA combinations for re-treatment were selected on an individual basis. In the present analysis, patient characteristics and rescue-regimens after virologic failure mainly based on first generation DAAs are described. Patients and methods Data were obtained from the German Hepatitis C-Registry (DHC-R), which is a national multicenter real-world cohort currently including about 16 500 patients recruited by more than 250 centers. The present analysis is based on 6683 patients who initiated a DAA therapy and for whom follow-up data (per-protocol analysis) were available. Results Among the patients, 188 (2.8 %) experienced a virologic relapse. Compared to SVR-patients, relapse patients were significantly more often male (77.7 % versus 56.9 %, respectively, p < 0.001), showed cirrhosis significantly more (48.4 % versus 28.1 %, respectively, p < 0.001) and a prior interferon-containing therapy (46.3 % versus 39.0 %, respectively, p = 0.049). The majority of patients who relapsed were infected with genotype 1 (47.4 %) followed by genotype 3 (29.8 %), and 95 relapse patients started DAA re-treatment. Characteristics of patients with rescue-treatment are similar to these of patients with relapse after initial DAA treatment. Thirty-one of 39 patients with complete follow-up data achieved SVR (79.5 %), and 8 patients had a relapse again (20.5 %). Patients who received rescue treatment including a new DAA class according to guidelines, except patients who received VOX/VEL/SOF, showed higher SVR rates than the entire group (21/25, 84 %). All patients who received VOX/VEL/SOF achieved SVR (n = 4, 100 %). Conclusions Patients with failure with DAA combination therapies are a difficult but urgent to treat population with the frequent presence of cirrhosis and prior treatment failure with interferon-based therapies. Rescue therapy with inclusion of a new DAA class leads to high SVR rates, but multiple targeted therapy with VOX/VEL/SOF seems to be most effective.

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Section: Discussionsupporting

confidence: 84%

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy – data from the German hepatitis C registry (DHC-R)

et al. 2020

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“…A previous study analyzed outcomes of 31 patients who experienced treatment failure on interferon‐free DAA‐based regimens and were retreated with genotype‐based DAA regimens without RAS testing guidance and reported an SVR rate of 86% 10 . This discordance with our results may be due to the fact that in this study, the majority of patients (48%) had failed a primary therapy with a combination of paritaprevir, ombitasvir, and dasabuvir and had been retreated with genotype‐specific drugs, most commonly sofosbuvir and ledipasvir with or without ribavirin.…”

Section: Discussionmentioning

confidence: 99%

“…There is a paucity of data on the sustained virological response at 12 weeks (SVR12) with re‐treatment regimens 9,10 . Drugs like voxilaprevir, glecaprevir, and pibrentasvir are expensive and not available in many countries.…”

Section: Introductionmentioning

confidence: 99%

Real‐world re‐treatment outcomes of direct‐acting antiviral therapy failure in patients with chronic hepatitis C

Elhence

Singh

Anand

et al. 2021

Journal of Medical Virology

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Direct‐acting antiviral (DAA) drugs are associated with high (>95%) sustained virological response at 12 weeks (SVR12) in chronic hepatitis C (CHC) patients. There is a paucity of data regarding the characteristics and re‐treatment outcomes of DAA treatment failure patients. In a retrospective analysis of the prospectively collected database, we assessed the outcomes of re‐treatment among patients with previous DAA failure. Patients' characteristics, viral characteristics, including resistance‐associated substitutions (RAS) in a subgroup of patients, SVR12, and clinical outcomes were studied. Of 40 patients with DAA failure, among whom 36 were retreated, mean age was 45.7 years, 63.9% (n = 23) were male, 63.9% (n = 23) had a genotype‐3 infection and 63.9% (n = 23) were cirrhotic. The re‐treatment regimens included a combination of pan‐genotypic DAA, mainly sofosbuvir and velpatasvir with or without ribavirin. Three patients who declined retreatment and one who was still on treatment was excluded. For patients who completed re‐treatment, SVR12 was 100% irrespective of genotypes. SVR12 among genotype 3 was 75% (15 of 20) when lost to follow‐up was considered a treatment failure. Six patients died due to liver‐related causes, including five (83.3%) with hepatocellular carcinoma. RAS analysis in 17 randomly selected patients did not reveal any dominant substitutions in NS5A or NS5B region affecting SVR12, though several novel mutations were observed. In conclusion, re‐treatment of CHC patients with prior DAA failure using pan‐genotypic DAA is associated with high SVR12 rates irrespective of genotype or the presence of RAS.

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“…Some of the poor treatment naive patients are also given the option of less expensive alternate to DAA; the standard IFN and ribavirin therapy, in case their medical is not covered by the governmentbased fund. Therefore, ribavirin and IFN therapy is still important and relevant in developing countries (20,21,47,66). This study was designed to evaluate TLR4 signaling in innate immune response against HCV infection in patients who have undergone IFN and ribavirin therapy compared with treatment-naive and healthy controls and its role in induction of profibrotic microenvironment via proinflammatory signaling.…”

Section: Introductionmentioning

confidence: 99%

Induction of Profibrotic Microenvironment via TLR4 MyD88-Dependent and -Independent Inflammatory Signaling in Chronic Hepatitis C Virus Infection

et al. 2020

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Hepatitis C virus (HCV) is a well-known pathogen to establish chronic infection leading to end-stage liver disease. The destruction of liver tissues takes its roots under chronic inflammation and proinflammatory signaling in liver microenvironment. The viral proteins interact with certain pattern recognition receptors, including Toll-like receptors, activating the innate immune system to clear the virus. HCV achieves immune evasion through other mechanisms and induce a continuous inflammatory microenvironment via Kupffer cells and Hepatic Stellate cells. This promotes disease progression. The current study aims to elucidate that the role of Toll-like receptor 4 (TLR4) induced innate immune response in chronic inflammation in patients chronically infected with HCV. For this purpose, changes in downstream signaling cascade of TLR4 during chronic HCV infection using peripheral blood mononuclear cells of chronic HCV patients were studied. We found significant increase in expression levels of proinflammatory and profibrotic genes induced by TLR4 Myeloid differentiation factor 88 (MyD88)-dependent pathway between treatment naive and healthy controls, while no significant difference between the expressions of genes involved in TLR4 signaling was found between treatment responders and healthy controls. Interestingly, both TLR4 MyD88-dependent and-independent pathways were found to be operational in nonresponders to interferon treatment. This further strengthens the involvement of innate immune signaling as a leading factor in HCV-mediated liver disease progression and the role of TLR4 MyD88-dependent and-independent pathway in ensuring the conditions for chronic inflammation.

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Real World Experience of Chronic Hepatitis C Retreatment with Genotype Specific Regimens in Nonresponders to Previous Interferon-Free Therapy

Cited by 15 publications

References 34 publications

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy – data from the German hepatitis C registry (DHC-R)

Treatment-failure to direct antiviral HCV regimens in real world: frequency, patient characteristics and rescue therapy – data from the German hepatitis C registry (DHC-R)

Real‐world re‐treatment outcomes of direct‐acting antiviral therapy failure in patients with chronic hepatitis C

Induction of Profibrotic Microenvironment via TLR4 MyD88-Dependent and -Independent Inflammatory Signaling in Chronic Hepatitis C Virus Infection

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