Risk of infections during interferon‐based treatment in patients with chronic hepatitis C virus infection and advanced hepatic fibrosis

Maan, Raoel; Meer, Adriaan J. van der; Hansen, Bettina E.; Feld, Jordan J.; Wedemeyer, Heiner; Dufour, Jean–François; Lammert, Frank; Manns, Michael P.; Zeuzem, Stefan; Janssen, Harry L A; Knegt, Robert J. de; Veldt, Bart J.

doi:10.1111/jgh.12929

Cited by 5 publications

(15 citation statements)

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“…The independent factors that drove the risk for infection in our study were female sex, DM and COPD, but not neutropenia. The association of female sex with infections during CHC therapy has been reported previously and was explained by a higher incidence of urinary tract infections (UTI) or vaginal infections [13,27]. Our findings are in agreement with these studies as 14% of clinically relevant infections were UTIs or vaginal infections (n=26) and 92% of these were observed in females.…”

Section: Discussionsupporting

confidence: 83%

“…Diabetes mellitus is a known risk factor for infection, but it is also associated with CHC [33]. A higher infection rate in diabetic CHC patients was therefore hypothesized and could be explained by various factors, such as vascular insufficiency and impaired leucocyte function in these patients [12,13,34,35]. Our study implies that diabetic patients should be monitored for infection during CHC therapy.…”

Section: Discussionmentioning

confidence: 99%

“…The risk factors in our study (female sex, DM and COPD) are factors that cannot be influenced and are not related to [12,13,36,37]. It is therefore likely that they remain risk factors for infection in future IFN-containing CHC regimes, thus these patients should be monitored carefully for infection during any PegIFN based regime.…”

Section: Discussionmentioning

confidence: 99%

“…However, prior studies in CHC patients undergoing (Peg)IFN and ribavirin J Gastrointestin Liver Dis, June 2016 Vol. 25 (RBV) therapy did not find an association between treatmentinduced neutropenia and infections, while dose reductions of PegIFN can reduce effectiveness [12][13][14][15][16][17]. The situation may be different with triple therapy, because phase III studies found that the inclusion of boceprevir to the CHC treatment strategy increased the likelihood of neutropenia compared to PegIFN and RBV [18,19].…”

Section: Introductionmentioning

confidence: 98%

“…Moderate and severe infections were considered clinically relevant. Based on the thresholds for dose reduction and treatment discontinuation of PegIFN, we distinguished three categories of neutropenia: severe if absolute neutrophil count (ANC) was below 500/µL, moderate if ANC was between 500 and 750/µL and mild if ANC was between 750 and 1500/µL [13,25]. We used Fib-4 > 3.25 to classify patients as cirrhosis, because of its high performance in detecting cirrhosis and high availability of included biomarkers in the general population [26].…”

Section: Outcomes and Definitionsmentioning

confidence: 99%

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High Risk of Infection During Triple Therapy with First- Generation Protease Inhibitors: A Nationwide Cohort Study

Berden

Zwietering

Maan

et al. 2016

JGLD

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Background & Aims: Peginterferon (PegIFN) remains the backbone of therapy for chronic hepatitis C (CHC) in economically constrained regions. However, PegIFN may cause neutropenia and addition of a protease inhibitor can increase the likelihood of neutropenia. The aims of this study were to assess the occurrence of clinically relevant infections during first-generation protease inhibitor based therapy and its risk factors as well as the relation to treatment-induced neutropenia. Methods: This multicenter (n=45) retrospective cohort study included CHC patients treated in the Netherlands. Based on absolute neutrophil count, categories of neutropenia were defined as: severe (<500/μL), moderate (500-750/μL) and mild (750-1500/μL). Likewise, infections were classified as severe (intravenous antibiotics/ hospitalization) and moderate (anti-infective treatment). We assessed risk factors for infections using multivariable regression analysis adjusting for multiple measurements. Results: We included 467 CHC patients, 319 (68%) were male and 111 (24%) had cirrhosis. A total of 185 clinically relevant infections (34 severe) occurred in 145 patients (31%). During treatment 310 patients experienced neutropenia (severe, n=34). Multivariable analysis identified female sex (OR 1.7, 95%CI 1.2- 2.5), chronic obstructive pulmonary disease (COPD) (OR 2.7, 95%CI 1.6- 4.5) and diabetes mellitus (OR 1.7, 95%CI 1.0-3.0) as risk factors for infections. Neutropenia at the previous visit was not associated with infection (univariable analysis: OR 0.9, 95%CI 0.6-1.3). Conclusion: This study shows that therapy with first generation protease inhibitors was complicated by an infection in 31% of patients. Not neutropenia, but female sex, COPD and diabetes mellitus were independent risk factors for infection. These patients should be monitored carefully once a PegIFN regimen is initiated. Abbreviations: ANC: absolute neutrophil count; CHC: chronic hepatitis C; COPD: chronic obstructive pulmonary disease; DAAs: direct acting antivirals; DM: diabetes mellitus; HCV: hepatitis C virus; PegIFN: pegylated interferon alpha; PI: protease inhibitor; UTI: urinary tract infection.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Outcomes and Definitionsmentioning

confidence: 99%

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High Risk of Infection During Triple Therapy with First- Generation Protease Inhibitors: A Nationwide Cohort Study

Berden

Zwietering

Maan

et al. 2016

JGLD

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Diskitis, Osteomyelitis, Spinal Epidural Abscess, Meningitis, and Endocarditis Following Sacroiliac Joint Injection for the Treatment of Low-Back Pain in a Patient on Therapy for Hepatitis C Virus

Nagpal

Flaherty

Benzon

2017

Regional Anesthesia and Pain Medicine

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Immunocompromised patients should be identified prior to treatment, and the small possibility of devastating complications should be thoughtfully weighed against the potential benefit of the procedure. Conservative management should be maximized initially, and if a procedure is done, strict asepsis must be maintained. Prophylaxis for S. aureus should be considered for immunocompromised patients undergoing interventional spine procedures.

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Risk factors for thiopurine‐induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype

Broekman

Coenen²,

Wanten

et al. 2017

Aliment Pharmacol Ther

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SummaryBackgroundLeucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S‐methyltransferase (TPMT) gene are the best‐known risk factor, but only explain up to 25% of leucopenia cases.AimTo identify the clinical risk factors for thiopurine‐induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections.MethodsPost hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial. For this analysis, patients without a variant in TPMT (*2, *3A or*3C) were included. Uni‐ and multivariate Cox‐proportional hazard models were used to identify risk factors for leucopenia and infections. Leucopenia was defined as a white blood cell (WBC) count <3.0 × 109/L and infections were classified according to the Common Terminology Criteria for Adverse Events.ResultsSixty hundred and ninety‐five patients (90.6%) included in the TOPIC‐trial had no variant in TPMT, of which 45 (6.5%) developed leucopenia. Median time to leucopenia was 56 (29‐112) days. Multivariate analysis showed that use of mercaptopurine compared to azathioprine was associated with leucopenia (hazard ratio [HR] 2.61 [95% CIs, 1.39‐4.88; P < .01]) and a higher baseline WBC count was protective (HR 0.80 [95% CIs, 0.71‐0.89; P < .01]). Risk factors for infections were older age (per 10 year; HR 2.07 [95% CIs, 1.18‐3.63; P = .01]) and concomitant use of biologic drugs (HR 2.15 [95% CIs, 1.14‐4.07; P = .02]).ConclusionsLow baseline WBC count and mercaptopurine, due to a relatively higher dose, were risk factors for thiopurine‐induced leucopenia in patients without a TPMT variant.

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Risk of infections during interferon‐based treatment in patients with chronic hepatitis C virus infection and advanced hepatic fibrosis

Cited by 5 publications

References 35 publications

High Risk of Infection During Triple Therapy with First- Generation Protease Inhibitors: A Nationwide Cohort Study

High Risk of Infection During Triple Therapy with First- Generation Protease Inhibitors: A Nationwide Cohort Study

Diskitis, Osteomyelitis, Spinal Epidural Abscess, Meningitis, and Endocarditis Following Sacroiliac Joint Injection for the Treatment of Low-Back Pain in a Patient on Therapy for Hepatitis C Virus

Risk factors for thiopurine‐induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype

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