Clinical Predictors Impacting Cryptococcal Dissemination and Poor Outcome in Patients With Cirrhosis

Jia-Hui Cheng; Ching-Wan Yip; Ying-Kui Jiang; Ling-Hong Zhou; Chun-Xing Que; Yu Luo; Xuan Wang; Hua-Zhen Zhao; Li-Ping Zhu

doi:10.1093/ofid/ofab296

Clinical Predictors Impacting Cryptococcal Dissemination and Poor Outcome in Patients With Cirrhosis

Open Forum Infect Dis. 2021 Jun 5;8(7):ofab296. doi: 10.1093/ofid/ofab296. eCollection 2021 Jul.

Authors

Jia-Hui Cheng¹, Ching-Wan Yip¹, Ying-Kui Jiang¹, Ling-Hong Zhou¹, Chun-Xing Que¹, Yu Luo¹, Xuan Wang¹, Hua-Zhen Zhao¹, Li-Ping Zhu^{1

2}

Affiliations

¹ Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
² Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China.

Abstract

Background: Cirrhosis is an end-stage liver disease and is reported as an independent risk factor for cryptococcosis. Information about cryptococcosis in patients with cirrhosis remains sparse.

Methods: Human immunodeficiency virus-uninfected patients with cryptococcosis and cirrhosis admitted to Huashan Hospital from July 2005 to June 2020 were reviewed. Efficacy and safety of antifungal treatments, clinical outcome, and prognostic factors of mortality were evaluated.

Results: A total of 49 cryptococcosis patients with cirrhosis were included. Sites of infection involved central nervous system (n = 38), lung (n = 21), bloodstream (n = 11), skin (n = 1), and bone (n = 1). Nine patients (18.4%) had pulmonary cryptococcosis alone. Viral hepatitis B infection (57.1%) was the most common cause of cirrhosis. Patients with decompensated cirrhosis (Child-Pugh class B and C) were more likely to have extrapulmonary cryptococcosis than those with compensated cirrhosis (90.7% vs 64.7%; P = .049). In patients with cryptococcal meningitis (CM), 7 were treated with amphotericin B with/without flucytosine, 5 with amphotericin B plus fluconazole with/without flucytosine, and 12 with fluconazole with/without flucytosine. Fluconazole (>400 mg/day) was well tolerated and only 1 patient had a mild adverse drug reaction. At 1-year follow-up, all patients treated with fluconazole with or without flucytosine survived, whereas the mortality rate was 14.3%-20.0% in the remaining groups. In addition, Child-Pugh class C cirrhosis (hazard ratio [HR], 7.555 [95% confidence interval {CI}, 1.393-40.971]) and time to diagnosis >120 days (HR, 18.619 [95% CI, 2.117-163.745]) were independent factors for 1-year mortality in patients with CM.

Conclusions: Severity of cirrhosis was associated with developing extrapulmonary cryptococcosis and mortality in CM. Early diagnosis and intervention of cryptococcosis are key for outcome.

Keywords: cryptococcal meningitis; cryptococcosis; extrapulmonary cryptococcosis; liver cirrhosis; pulmonary cryptococcosis.