The Changing Paradigm of Management of Liver Abscesses in Chronic Granulomatous Disease

Abstract

Background: Chronic granulomatous disease (CGD) is a rare genetic disorder causing recurrent infections. More than one-quarter of patients develop hepatic abscesses and liver dysfunction. Recent reports suggest that disease-modifying treatment with corticosteroids is effective for these abscesses. Comparison of corticosteroid therapy to traditional invasive treatments has not been performed.

Methods: Records of 268 patients with CGD treated at the National Institutes of Health from 1980 to 2014 were reviewed. Patients with liver involvement and complete records were included. We recorded residual reactive oxygen intermediate (ROI) production by neutrophils, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase germline mutation status, laboratory values, imaging characteristics, time to repeat hepatic interventions, and overall survival among 3 treatment cohorts: open liver surgery (OS), percutaneous liver-directed interventional radiology therapy (IR), and high-dose corticosteroid management (CM).

Results: Eighty-eight of 268 patients with CGD suffered liver involvement. Twenty-six patients with a median follow-up of 15.5 years (8.5-32.9 years of follow-up) had complete records and underwent 100 standard interventions (42 IR and 58 OS). Eight patients received a treatment with high-dose corticosteroids only. There were no differences in NADPH genotype, size, or number of abscesses between patients treated with OS, IR, or CM. Time to repeat intervention was extended in OS compared with IR (18.8 vs 9.5 months, P = .04) and further increased in CM alone (median time to recurrence not met). Impaired macrophage and neutrophil function measured by ROI production correlated with shorter time to repeat intervention (r = 0.6, P = .0019).

Conclusions: Treatment of CGD-associated liver abscesses with corticosteroids was associated with fewer subsequent hepatic interventions and improved outcome compared to invasive treatments.

Figure 1.

Patient inclusion schema. Thirty-two of 268 chronic granulomatous disease (CGD) patients were eligible for analysis based on the criteria of (1) having a history of CGD liver involvement and (2) having complete, uninterrupted follow-up of their CGD liver care available within National Institutes of Health medical records. Abbreviations: BMT, bone marrow transplant; CGD, chronic granulomatous disease; CM, high-dose corticosteroid management; IR, interventional radiology; NIH, National Institutes of Health; OS, open surgery.

Figure 2.

A, Magnetic resonance image showing a 2-cm abscess (arrow) in the right anterior sector of the liver of a 22-year old male patient with chronic granulomatous disease (CGD) treated with multiple courses of antibiotics. Aspirate grew Staphylococcus aureus and he eventually underwent nonanatomical wedge resection. B, New 2-cm abscess (arrow) in the right posterior sector in the same patient 13 months later.

Figure 3.

Kaplan-Meier curves showing time to repeat hepatic intervention (A) for the 2 standard interventions, interventional radiology (IR) or open surgery (OS). B, Overall survival rates from time of last intervention; comparisons of survival curves by log-rank (Mantel-Cox) test, 2-tailed P values. C, Time to repeat hepatic intervention (in months) of chronic granulomatous disease patients with liver abscesses managed with IR or OS vs patients managed with high-dose corticosteroids (CM). Patients who underwent operative (OS) or percutaneous (IR) management of liver abscesses are combined. D, Overall survival rates of patients who last underwent OS or IR procedures compared with patients who received CM as last intervention; log-rank (Mantel-Cox) test, 2-tailed P values.

Figure 4.

Computed tomography image revealing a 4.6-cm abscess in the right posterior sector (arrow) of the liver (A), and resolution of this abscess 20 months after high-dose corticosteroid therapy with antibiotics was commenced (B).

Figure 5.

A, Baseline residual reactive oxygen intermediate (ROI) levels (superoxide nmol/hour) are correlated with time to repeat hepatic intervention in patients with chronic granulomatous disease (CGD) with liver abscesses (Pearson product-moment correlation coefficient, r = 0.5999, 2-tailed P value). Surgical outcome measured by time to repeat hepatic intervention in CGD patients with liver abscesses by previously defined ROI quartiles (in superoxide nmol/hour) predictive of poor outcome (Q1 and Q2 [0.26–0.94 and 0.95–1.67, respectively] vs Q3 and Q4 [1.70–2.71 and 2.72–60.5, respectively]) (B), or by low vs high preoperative residual neutrophil function (ROI <2.3 nmol superoxide/hour [dashed line] vs ≥2.3 nmol superoxide/hour ROI levels) (C). Hepatic procedure-free interval (HPFI) mean of any hepatic intervention for each patient. Patients who received corticosteroids had similar baseline neutrophil function compared to patients who underwent interventional radiology (IR) or open surgery (OS) (D) (mean baseline ROI in neutrophils and monocytes, 2.12 nmol superoxide/10⁶ cells vs steroids, 1.64 nmol superoxide/10⁶; Mann-Whitney U test, 2-tailed P = .202).

Figure 6.

Multiloculation (A) and thickened pseudocapsule (B) (arrows) of liver abscesses observed in patients with chronic granulomatous disease (CGD) by contrast-enhanced magnetic resonance imaging.