Fungal infections in patients with chronic liver disease: mortality and associated risk factors
Keywords:Chronic liver disease, Fungal infection, Liver cirrhosis, Mortality
Background: Patients with chronic liver disease are immunocompromised and prone to different opportunistic infections. Fungal infections in patients admitted with liver cirrhosis are not rare and they may increase mortality and morbidity of these patients. Aims of the study is to determine the mortality and its risk factors associated with fungal infections in patients with chronic liver disease.
Methods: In this retrospective study, patients admitted with chronic liver disease during the last four years on this hospital were studied for diagnosed fungal infections. A matched control group of cirrhosis patients with a ratio of 1:2 admitted without fungal infections was also studied and mortality was compared between the two groups.
Results: Seventy admitted patients of liver cirrhosis with microbial and histopathological evidence of fungal infection were found while 140 patients of the control group had no evidence of fungal infection. Hepatitis C virus infection was the major cause of cirrhosis (65%) and most of the patients were in child class C(63%). Urinary tract infection, esophageal candidiasis, and mucormycosis were major fungal infections. Mortality was much higher in the fungal infections group (34.3%) as compared to the non-infectious group (16%). On multivariate analysis, high WBCs count, hypo-albuminemia and high creatinine levels were the worst factors affecting mortality.
Conclusions: Fungal infections are a significant cause of morbidity and mortality in patients with decompensated cirrhosis. Advanced cirrhosis, renal insufficiency, and leucocytosis are independent predictors of fatal outcome in these patients.
Alexopoulou A, Vasilieva L, Agiasotelli D, Dourakis SP. Fungal infections in patients with cirrhosis. J Hepatol 2015 Oct;63(4):1043-5.
Arvaniti V, D'Amico G, Fede G, Manousou P, Tsochatzis E, Pleguezuelo M, et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterol. 2010 Oct 1;139(4):1246-56.
Bajaj JS, Liu EJ, Kheradman R, Fagan A, Heuman DM, White M, et al. Fungal dysbiosis in cirrhosis. Gut. 2018 Jun 1;67(6):1146-54.
Bassetti M, Peghin M, Carnelutti A, Righi E, Merelli M, Ansaldi F, et al. Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study. Intensive Care Med. 2017 Apr 1;43(4):509-18.
Bonnel AR, Bunchorntavakul C, Reddy KR. Immune dysfunction and infections in patients with cirrhosis. Clinical gastroenterology and hepatology. 2011 Sep 1;9(9):727-38.
Borzio M, Salerno F, Piantoni L, Cazzaniga M, Angeli P, Bissoli F, et al. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study. Digest Liver Dis. 2001 Feb 1;33(1):41-8.
Christou L, Pappas G, Falagas ME. Bacterial infection-related morbidity and mortality in cirrhosis. Am J Gastroenterol. 2007 Jul;102(7):1510.
Fernández J, Acevedo J, Castro M, Garcia O, Rodríguez de Lope C, Roca D, Pavesi M, Sola E, Moreira L, Silva A, Seva‐Pereira T. Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatol. 2012 May;55(5):1551-61.
Fernández J, Navasa M, Gómez J, Colmenero J, Vila J, Arroyo V, et al. Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis. Hepatol. 2002 Jan;35(1):140-8.
Ferri C, Antonelli A, Mascia MT, Sebastiani M, Fallahi P, Ferrari D, et al. HCV-related autoimmune and neoplastic disorders: the HCV syndrome. Digest Liver Dis. 2007 Sep 1;39:S13-21.
Garcia-Tsao G, Wiest R. Gut microflora in the pathogenesis of the complications of cirrhosis. Best Practice Res Clin Gastroenterol. 2004 Apr 1;18(2):353-72.
Ghassemi S, Garcia-Tsao G. Prevention and treatment of infections in patients with cirrhosis. Best Practice Res Clin Gastroenterol. 2007 Jan 1;21(1):77-93.
Gustot T, Durand F, Lebrec D, Vincent JL, Moreau R. Severe sepsis in cirrhosis. Hepatol. 2009 Dec;50(6):2022-33.
Jean SS, Fang CT, Shau WY, Chen YC, Chang SC, Hsueh PR, Hung CC, Luh KT. Cryptococcaemia: clinical features and prognostic factors. Qjm. 2002 Aug 1;95(8):511-8.
Karvellas CJ, Pink F, McPhail M, Austin M, Auzinger G, Bernal W, et al. Bacteremia, acute physiology and chronic health evaluation II and modified end stage liver disease are independent predictors of mortality in critically ill non transplanted patients with acute on chronic liver failure. Crit Care Med. 2010 Jan 1;38(1):121-6.
Lahmer T, Messer M, Mayr U, Saugel B, Noe S, Schultheiss C, et al. Fungal “colonisation” is associated with increased mortality in medical intensive care unit patients with liver cirrhosis. Mycopathologia. 2015 Feb 1;179(1-2):63-71.
Marchetti O, Eggimann P, Calandra T. Invasive candidiasis in critically ill patients: does progressing knowledge improve clinical management and outcome?. Curr Opinion Criti Care. 2010 Oct 1;16(5):442-4.
O'donohue J, Workman MR, Rolando N, Yates M, Philpott-Howard J, Williams R. Urinary tract infections in primary biliary cirrhosis and other chronic liver diseases. Eur J Clin Microbiol Infect Dis. 1997 Oct 1;16(10):743-6.
Puig-Asensio M, Pemán J, Zaragoza R, Garnacho-Montero J, Martín-Mazuelos E, Cuenca-Estrella M, Almirante B. Impact of therapeutic strategies on the prognosis of candidemia in the ICU. Crit Care Med. 2014 Jun 1;42(6):1423-32.
Rolando N, Philpott-Howard J, Williams R. Bacterial and fungal infection in acute liver failure. Semin Liver Dis 1996;16(4): 389-402.
Singh N, Husain S, de Vera M, Gayowski T, Cacciarelli TV. Cryptococcus neoformans infection in patients with cirrhosis, including liver transplant candidates. Med. 2004 May 1;83(3):188-92.
Tandon P, Garcia-Tsao G. Bacterial infections, sepsis, and multiorgan failure in cirrhosis. Semin Liver Dis 2008;28(1):26-42.
Tascini C, Menichetti F, Merelli M, Farese A, Sozio E, Scarparo C, Viaggi B, Rossolini GM, Bassetti M. Variable incidence of candidemia in patients admitted to ICUs or medical wards of large tertiary-care Italian hospitals. Clin Microbiol Infect. 2015 Sep 1;21(9):e71-2.
Wasmuth HE, Kunz D, Yagmur E, Timmer-Stranghöner A, Vidacek D, Siewert E, et al. Patients with acute on chronic liver failure display ‘sepsis-like’immune paralysis. J Hepatol. 2005 Feb 1;42(2):195-201.