Invasive aspergillosis in liver transplant recipients, an infectious complication with low incidence but significant mortality

Table 1 Demographic information and background factors before transplantation of the study population

Covariate	Case	Control	P value	OR (95%CI)
Gender (Male)	18 (81.8%)	31 (81.6%)	0.9	-
Gender (Female)	4 (18.2%)	7 (18.4%)	0.9	-
Age mean (SD)	45.27 (14.85)	47.21 (12.03)	0.58	-
MELD score (SD)	21.05 (6.78)	20.24 (5.54)	0.62	-
Pretransplant ICU stay	1.95 (0.22)	1.97 (0.16)	0.9	-
Duration of pretransplant ICU stay	2 (1)	1 (0)	0.27	-
Pretransplant creatinine	1.74 (1.03)	1.22 (0.47)	0.04	0.34 (0.13-0.87)
Pretransplant ventilator within 1 wk	-	1 (2.6%)	0.9	-
Pretransplant dialysis within 1 mo	-	1 (2.6%)	0.9	-
Pretransplant diabetes mellitus	12 (54.5%)	15 (39.5%)	0.26	-
Fulminant hepatic failure	6 (27.3%)	2 (5.3%)	0.18	-
Immunosuppressive agents (steroids)	2 (9.1%)	6 (15.8%)	0.08	-
Immunosuppressive agent (antimetabolites)	1 (4.5%)	1 (2.6%)	0.08	-
Immunosuppressive agent (steroids & antimetabolites)	1 (4.5%)	0	0.08	-
Immunosuppressive agent (steroids & calcineurin inhibitors)	1 (4.5%)	0	0.08	-
Immunosuppressive agent (no)	12 (54.5%)	31 (81.6%)	0.08	-
The pretransplant episode of documented bacterial peritonitis	3 (13.6%)	5 (13.2%)	0.9	-
Previous systemic antibiotic use of more than 14 consecutive days	5 (22.7%)	6 (15.8%)	0.51	-
Re transplantation	5 (22.7%)	3 (7.9%)	0.13	-

CI: Confidence interval; ICU: Intensive care unit; OR: Odds ratio; SD: Standard deviation.

Table 2 Clinical and laboratory information of patients with invasive aspergillus infection¹

Covariate	Number (percent)
Diagnosis (proven)	9 (40.9%)
Diagnosis (probable)	13 (59.1%)
Site of diagnosis (isolated pulmonary)	19 (86.4%)
Site of diagnosis (isolated sinusitis)	2 (9.1%)
Site of diagnosis (peritonitis)	1 (4.5%)
Positive galactomannan (serum)	5 (22.7%)
Positive galactomannan (BAL)	8 (36.4%)
Positive galactomannan (N/A)	9 (40.9%)
PCR (positive)	8 (36.4%)
PCR (negative)	3 (13.6%)
PCR (N/A)	11 (50%)
Pathology (positive)	2 (9.1%)
Pathology (negative)	4 (18.2%)
Pathology (N/A)	16 (72.7%)
Fungal culture (positive)	10 (45.5%)
Fungal culture (negative)	2 (9.1%)
Fungal culture (N/A)	10 (45.5%)
Site of positive culture (sputum)	2 (9.1%)
Site of positive culture (BAL)	6 (27.3%)
Site of positive culture (sinus biopsy)	4 (18.2%)
Site of positive culture (pulmonary biopsy)	1 (4.5%)
Site of positive culture (peritonitis)	1 (4.5%)
CT scan findings (nodules)	11 (50%)
CT scan findings (ground glass opacity)	2 (9.1%)
CT scan findings (halo sign)	10 (45.5%)
CT scan findings (consolidation)	5 (22.7%)
CT scan findings (cavity)	3 (13.6%)
CT scan findings (pleural effusion)	7 (31.8%)
Treatment response at 6 & 12 wk (cure)	10 (45.5%)
Treatment response at 6 & 12 wk (partial response)	4 (18.2%)
Treatment response at 6 & 12 wk (stable)	-
Treatment response at 6 & 12 wk (progression)	-
Treatment response at 6 & 12 wk (death)	8 (36.4%)
12- month mortality	10 (4.45%)

¹Cases information are attached.

BAL: Bronchoalveolar lavage; CT: Computed tomography; PCR: Polymerase chain reaction; N/A: Not applicable.

Table 3 Comparison of factors related to the transplant of the study population

Covariate	Case	Control	P value	OR (95%CI)
Type of anastomosis (duct to duct)	16 (72.7%)	30 (78.9%)	0.53	-
Type of anastomosis (Roux-en-Y)	6 (27.3%)	8 (21.1%)	0.53	-
Cold ischemic time (h)	283.95 (66.58)	300.37 (58.39)	0.32	-
Underlying disease (NASH)	6 (27.3%)	6 (15.8%)	0.74	-
Underlying disease (PSC)	3 (13.6%)	8 (21.1%)	0.74	-
Underlying disease (HBV)	3 (13.6%)	5 (13.2%)	0.74	-
Underlying disease (HCV)	2 (9.1%)	1 (2.6%)	0.74	-
Underlying disease (AIH)	1 (4.5%)	3 (7.9%)	0.74	-
Underlying disease (AIH & HCC)	1 (4.5%)	1 (2.6%)	0.74	-
Underlying disease (HCV & NASH)	1 (4.5%)	-	0.74	-
Underlying disease (PBC)	1 (4.5%)	-	0.74	-
Underlying disease (Others)	4 (18.1%)	5 (13.2%)	0.74	-
Underlying disease (ASH)	-	2 (5.3%)	0.74	-
Underlying disease (HCV & HCC)	-	2 (5.3%)	0.74	-
Underlying disease (NASH & HCC)	-	2 (5.3%)	0.74	-
Underlying disease (NASH & PSC)	-	1 (2.6%)	-	-
Underlying disease (HBV & HCC)	-	1 (2.6%)	-	-
Underlying disease (Wilson)	-	1 (2.6%)	-	-
Intraoperative blood transfusion	3.45 (3.05)	2.5 (2.57)	0.2	-
Induction therapy (ATG)	8 (36.4%)	6 (15.8%)	< 0.001	0.08 (0.02-0.41)
Induction therapy (methyl prednisolon)	14 (63.6%)	32 (84.2%)	< 0.001	0.05 (0.01-0.25)
Biliary leak post-transplant	9 (40.9%)	-	< 0.001	-
Reoperation within 30 d of transplant	12 (54.5%)	5 (13.2%)	< 0.001	7.92 (2.25-27.94)
Hepatic artery thrombosis post-transplant	8 (36.4%)	1 (2.6%)	< 0.001	21.14 (2.42-184.79)

AIH: Autoimmune Hepatitis; ASH: Alcoholic Steatohepatitis; ATG: Antithymocyte Globulin; HBV: Hepatitis B Virus; HCC: Hepatocellular Carcinoma; HCV: Hepatitis C Virus; NASH: Nonalcoholic Steatohepatitis; PBC: Primary Biliary Cirrhosis; PSC: Primary Sclerosing Cholangitis; CI: Confidence interval; OR: Odds ratio.

Table 4 Comparison of the post-transplant factors in the study population

Covariate	Case	Control	P value	OR (95%CI)
Antifungal prophylaxis after transplant (Fluconazole)	10 (45.5%)	13 (34.2%)	0.003	0.20 (0.05-0.85)
Antifungal prophylaxis after transplant (voriconazole)	9 (40.9%)	5 (13.1%)		0.08 (0.02-0.43)
Antifungal prophylaxis after transplant (no)	3 (13.6%)	20 (52.7%)		-
Bacteremia within 2 wk before diagnosis	3 (13.6%)	4 (10.5%)	0.70	-
Pneumonia within 2 wk before diagnosis	13 (59.1%)	4 (10.5%)	< 0.001	0.08 (0.02-0.31)
Systemic antibacterial within 2 wk before diagnosis	16 (72.7%)	15 (39.5%)	< 0.001	4.09 (1.31-12.81)
Dialysis requirement	7 (31.8%)	4 (10.5%)	0.08
CMV viremia before diagnosis	9 (40.9%)	4 (10.5%)	0.009	5.89 (1.54-22.47)
CMV diseases before diagnosis	3 (13.6%)	2 (5.3%)	0.35
Length of ICU stay at the time of transplant	4.05 (3.59)	1.75 (1.20)	0.008	0.56 (0.38-0.82)
Duration of mechanical ventilation at the time of transplant	1.25 (0.55)	1.12 (0.41)	0.34
Creatinine at the day of diagnosis (highest value)	1/87 (SD:1/1)	1/21 (SD:1/43)	-	-

CI: Confidence interval; CMV: Cytomegalovirus; ICU: Intensive care unit; OR: Odds ratio; SD: Standard deviation.

Table 5 Rejection before and after diagnosis of invasive aspergillosis

Covariate	Case	Control	P value	OR (95%CI)
Rejection requiring treatment within 3 mo before diagnosis	13 (59.1%)	10 (26.3%)	0.01	4.04 (1.33-12.34)
Rejection required treatment after diagnosis	4 (18.2%)	4 (10.5%)	0.45	-

CI: Confidence interval; OR: Odds ratio.