P406 Rise in HIV negative Cryptococcal infection in liver disease patient: epidemiology, risk factor, antifungal susceptibility profile from tertiary care hepatobiliary center
Authors: Patel Dhruvi , Kale Pratibha , Khillan Vikas , Sarin Shiv Kumar 
Published: September 2022

Abstract

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM

Objective
Cryptococcus neoformans is an encapsulated yeast found ubiquitously in the environment, considered important in immunocompromised individuals with HIV. Non-HIV susceptible groups include malignancies, long-term use of corticosteroids, solid organ transplantation, sarcoidosis, immunosuppressive therapy, and cirrhosis. Cryptococcal infections are rising in HIV-negative cirrhotic patients, accounting for 6-21% of the systemic infections. Chronic liver disease (CLD) is a neglected risk factor for fungal infections. To analyze epidemiology, risk factors, and antifungal susceptibility profile of HIV-negative liver disease patients.

Material Methods
The retrospective study was conducted in tertiary care hepatobiliary center in New Delhi, India from January 2017 to March 2022 after ethical approval. Demographic data, laboratory data, and clinical history of the patients admitted with liver disease and suspected cryptococcal infections were obtained from Hospital records for epidemiology and risk factor analysis. Blood, CSF, serum, urine, and body fluid (Ascitic fluid, peritoneal fluid, pleural fluid, MiniBAL) samples were processed for fungal culture on SDA and SDA with cyclohexamide. Blood and body fluid were also inoculated in an automated blood culture system (BacT/ALERT 3D bioMérieux). Samples were processed for gram stain, India ink, and Cryptococcal antigen. Identification was done by an automated identification system (VITEK 2 compact bioMérieux). The micro-broth dilution method (Sensititre YeastOne colorimetric plate, Thermo Fisher Scientific, MA, United States) was used to determine the susceptibility of all Cryptococcus strains to the six antifungal drugs, fluconazole, 5-fluorocytosine, amphotericin B, itraconazole, posaconazole, and voriconazole. The results were reported as wild-type (WT) or non-wild-type (non-WT) in accordance with the epidemiological cutoff value (ECV) set for Cryptococcus spp. (Espinel-Ingroff et al., 2012a, b; CLSI, 2018).

Results
We analyzed 30 patients of suspected cryptococcal infection and obtained 40 C. neoformans isolates from different samples from these patients. Out of 40 samples, C neoformans was isolated from blood (25,62.5%), urine (6,15%), ascitic fluid (4,10%), mini-BAL (2,5%), bone marrow (1,2.5%), CSF (1,2.5%), pleural fluid (1,2.5%). All samples were positive for Cryptococcal antigen. India ink positivity was observed in 56%. Alcoholic liver disease was the most common risk predictive factor seen in 30% of patients. Hepatitis B and C-associated with CLD was seen in 20%. Other risk predictive factors were AKI (70%), diabetes mellitus (20%), TB (10%), autoimmune hepatitis (6.6%), autoimmune disease (autoimmune hemolytic anemia, Sjogren syndrome) (6.6%), Sarcoidosis (3.3%), Hepatocellular carcinoma (3.3%), HIV (3.3%). Hepatic encephalopathy was seen in 70% of patients which mimics the symptoms of C. meningitis.7.5% (3/40), 5% (2/40), 2.5% (1/40), 7.5% (3/40), and 2.5% (1/40) of C. neoformans strains were non-WT to fluconazole, 5-fluorocytosine, amphotericin B, posaconazole, and itraconazole, respectively, but all strains were WT to voriconazole. Overall mortality was 66.6%.

Conclusion
Above study shows that liver diseases are an important risk factor for cryptococcal infection owing to immunosuppressed state, use of steroids, and associated comorbidities like DM, TB, AKI, autoimmune disease, Sarcoidosis, hepatocellular carcinoma. Therefore, it is necessary to investigate and be vigilant about the isolation of Cryptococcus. The use of appropriate antifungals can improve clinical outcomes. As there is increasing resistance to amphotericin B, 5-fluorocytosine, azoles; antifungal susceptibility testing should be done. Cryptococcal antigen detection can be useful in non-CSF samples as well.