Long-term Efficacy of Interferon-Free Antiviral Treatment Regimens in Patients With Hepatitis C Virus–Associated Cryoglobulinemia Vasculitis

Cacoub, Patrice; Ahmed, Si Nafa Si; Ferfar, Yasmina; Pol, Stanislas; Thabut, Dominique; Hézode, Christophe; Alric, Laurent; Comarmond, Cloé; Ragab, Gafaar; Quartuccio, Luca; Hegazy, Mohamed Tharwat; Poynard, Thierry; Rigon, Matthieu Resche; Saadoun, David

doi:10.1016/j.cgh.2018.05.021

Cited by 76 publications

(79 citation statements)

References 42 publications

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“…The findings highlight the causal role of active HCV in these conditions and the role of DAA‐related SVR as a preventive measure. The findings also support growing literature about successful DAA treatment and resolution of mixed cryoglobulinaemia vasculitis with or without renal involvement with minimum side effects and a mechanism related to changes in peripheral B‐ and T‐cell homoeostasis . A previous study with a similar design conducted using national VA data among patients receiving interferon‐based HCV therapy reported risk reductions when patients with SVR were compared with treated patients without SVR for mixed cryoglobulinaemia, glomerulonephritis, porphyria cutanea tarda and diabetes but not NHL …”

Section: Discussionsupporting

confidence: 80%

The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection

El–Serag

Christie

Puenpatom

et al. 2019

Aliment Pharmacol Ther

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Background: Direct-acting anti-viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited. Aim: To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV. Methods: We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models. Results: Of the 45 260 patients treated with DAA with mean follow-up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/ 1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10-0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41-0.90) and lichen planus (aHR = 0.46; 95% CI 0.30-0.70), but not for non-Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52-1.43) or diabetes (aHR = 0.98; 95% CI 0.81-1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11-1.03). Conclusions: Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non-Hodgkin's lymphoma or diabetes. Additional supporting information will be found online in the Supporting Information section at the end of the article. How to cite this article: El-Serag HB, Christie IC, Puenpatom A, Castillo D, Kanwal F, Kramer JR. The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection.

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Section: Discussionsupporting

confidence: 80%

The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection

El–Serag

Christie

Puenpatom

et al. 2019

Aliment Pharmacol Ther

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“…These clonal B‐cells display peculiar characteristics such as low expression of CD21 (CD21 low B‐cells) and features of functional exhaustion . The eradication of HCV infection with direct‐acting antivirals (DAAs) is associated in most cases with healing of MCV and with regression of NHL, but cryoglobulins persist in almost half of HCV‐cured MC patients and clinical relapses have been observed in some of them …”

Section: Introductionmentioning

confidence: 99%

“…These clonal B-cells display peculiar characteristics such as low expression of CD21 (CD21 low B-cells) and features of functional exhaustion. [4][5][6] The eradication of HCV infection with direct-acting antivirals (DAAs) is associated in most cases with healing of MCV [7][8][9] and with regression of NHL, 10 but cryoglobulins persist in almost half of HCV-cured MC patients 8 and clinical relapses have been observed in some of them. 9,11 We previously reported 12 that circulating B-cell clones may persist for at least some months after the eradication of HCV, suggesting that this might be the cause for HCV-independent persistence or relapse of MC.…”

Section: Introductionmentioning

confidence: 99%

Long‐lasting persistence of large B‐cell clones in hepatitis C virus‐cured patients with complete response of mixed cryoglobulinaemia vasculitis

Visentini

Padre

Colantuono

et al. 2019

Liver International

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Background & Aims Hepatitis C virus (HCV)‐related mixed cryoglobulinaemia vasculitis (MCV) is characterized by the expansion of rheumatoid factor‐producing B‐cell clones. The aim of this study was to assess whether B‐cell clones may persist in these patients after the clearance of the virus with antiviral therapy, and whether their persistence influences clinical outcomes. Methods Forty‐five HCV‐cured MCV patients were followed up for a median of 18.5 (range 9‐38) months after the clearance of HCV. Circulating B‐cell clones were detected using flow cytometry either by the skewing of kappa/lambda ratio or by the expression of a VH1‐69‐encoded idiotype. Results The clinical response of vasculitis was 78% complete, 18% partial and 4% null. However, cryoglobulins remained detectable in 42% of patients for more than 12 months. Circulating B‐cell clones were detected in 18 of 45 patients, and in 17 of them persisted through the follow‐up; nine of the latter patients cleared cryoglobulins and had complete response of vasculitis. Several months later, two of these patients had relapse of MCV. Conclusions B‐cell clones persist in MCV patients long after HCV infection has been cleared but halt the production of pathogenic antibody. These ‘dormant’ cells may be reactivated by events that perturb B‐cell homeostasis and can give rise to the relapse of cryoglobulinaemic vasculitis.

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“…There is growing evidence that an SVR can provide measurable benefits also on extrahepatic complications of HCV, such as glycemic control, 14 vascular disease, 15 and crioglobulinemia. 16 In a recent prospective study from Carrat et al, 17 the achievement of an SVR following treatment with DAA has been associated with a significant decrease in all-cause mortality, including nonliver-related mortality (►Table 1). SVR has been associated with a significant reduction in the number of vascular events in two large French cohorts of HCV cirrhotic patients.…”

Section: Extrahepatic Diseasesmentioning

confidence: 98%

Postsustained Virological Response Management in Hepatitis C Patients

et al. 2020

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The introduction of direct-acting antiviral agents (DAA) has revolutionized management and care of patients with chronic hepatitis C virus (HCV) infection, leading to cure rates higher than 90% in patients with advanced liver disease as well. Viral eradication has been associated with longer survival, reduced mortality from both hepatic and extrahepatic causes, improvement in liver function, and reduced incidence of HCV-related extrahepatic diseases. While patients with mild fibrosis can safely be discharged after achievement of a sustained virological response, patients with advanced fibrosis and cirrhosis remain at risk of developing complications of liver disease, thus requiring regular and life-long surveillance. Major complications of cirrhosis that need to be monitored are hepatocellular carcinoma onset and development or progression of clinically significant portal hypertension.

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Long-term Efficacy of Interferon-Free Antiviral Treatment Regimens in Patients With Hepatitis C Virus–Associated Cryoglobulinemia Vasculitis

Cited by 76 publications

References 42 publications

The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection

The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection

Long‐lasting persistence of large B‐cell clones in hepatitis C virus‐cured patients with complete response of mixed cryoglobulinaemia vasculitis

Postsustained Virological Response Management in Hepatitis C Patients

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