Acute liver failure and death predictors in patients with dengue-induced severe hepatitis

Table 1 Laboratory profiles at initial presentation

Laboratory parameters	All DISH patients (n = 151)	DISH without ALF (n = 134)	DISH with ALF (n = 17)	P value
Hematocrit (%)	41.0 ± 7.8	41.1 ± 7.7	40.2 ± 8.8	0.833
WBC (× 103/μL)	5.6 ± 3.8	5.5 ± 3.8	6.3 ± 3.9	0.379
Neutrophil (× 103/μL)	3.2 ± 2.8	3.0 ± 2.7	4.5 ± 3.0	0.461
Lymphocyte (× 103/μL)	1.5 ± 1.1	1.6 ± 1.1	1.1 ± 7.0	0.461
AL (× 103/μL)	0.4 ± 0.7	0.4 ± 0.8	0.2 ± 0.2	0.501
Platelet (× 1012/μL)	56.9 ± 76.5	57.2 ± 75.0	54.9 ± 89.9	0.190
INR	1.4 ± 0.7	1.2 ± 0.3	2.4 ± 1.0	0.004c
Creatinine (mg/dL)	1.0 ± 1.0	0.9 ± 0.9	1.9 ± 1.4	0.134
Albumin (g/dL)	3.6 ± 0.6	3.7 ± 0.5	3.0 ± 0.5	0.136
Total bilirubin (mg/dL)	2.0 ± 4.6	1.4 ± 1.7	6.3 ± 11.5	0.272
SGOT (U/L)	1547.0 ± 2254.3	1130.6 ± 1302.5	4804.3 ± 4540.4	0.437
SGPT (U/L)	694.3 ± 725.1	590.8 ± 493.6	1510.5 ± 1451.6	0.369
ALP (U/L)	112.0 ± 105.5	108.7 ± 108.5	138.1 ± 75.7	0.157
MELD score	12.3 ± 8.3	9.7 ± 4.7	24.5 ± 10.2	< 0.001d

^cP < 0.005.

^dP < 0.001. AL: Atypical lymphocyte; DISH: Dengue-induced severe hepatitis; ALF: Acute liver failure; WBC: White blood cell; INR: International normalized ratio; SGOT: Serum glutamate-oxaloacetate transaminase; SGPT: Serum glutamate-pyruvate transaminase; ALP: Alkaline phosphatase; MELD: Model for End-Stage Liver Disease.

Table 2 Regression analysis of the factors associated with acute liver failure from dengue-induced severe hepatitis

Parameters	Univariate analysis			Multivariate analysis
	Odds ratio	95%CI	P value	Adjusted odds ratio	95%CI	P value
Baseline demographic information
Age	1	0.9-1.0	0.044a	0.9	0.9-1.0	0.033b
Male sex	0.7	0.3-2.1	0.57	3.9	0.5-30.1	0.193
Hematological parameters change with response to dengue severity
Hematocrit	1	0.9-1.0	0.624	-	-	-
WBC count	1	1.0-1.0	0.419	-	-	-
Percentage of neutrophils	1.1	1.0-1.1	0.001c	-	-	-
Platelet count	1	1.0-1.0	0.907	-	-	-
Liver status at diagnosis of DISH
Total bilirubin	1.3	1.0-1.6	0.026d	-	-	-
SGPT	1	1.0-1.0	0.001e	-	-	-
INR	23.7	5.0-111.9	< 0.001f	-	-	-
Albumin	0.1	0.04-0.4	< 0.001g	0.7	0.2-3.2	0.696
Creatinine	2.2	1.3-3.9	0.006h	-	-	-
MELD score	1.3	1.2-1.4	< 0.001i	1.3	1.1-1.5	< 0.001j
Presence of liver comorbidity	3.8	1.1-13.9	0.042k	4.5	0.4-48.6	0.215

^aP < 0.05.

^bP < 0.05.

^cP = 0.001.

^dP < 0.05.

^eP = 0.001.

^fP < 0.001.

^gP < 0.001.

^hP < 0.05.

ⁱP < 0.001.

^jP < 0.001.

^kP < 0.05. DISH: Dengue-induced severe hepatitis; WBC: White blood cell; INR: International normalized ratio; SGPT: Serum glutamate-pyruvate transaminase; MELD: Model for End-Stage Liver Disease; CI: Confidence interval.

Table 3 Regression analysis of the factors associated with death from dengue-induced severe hepatitis

Parameters	Univariate analysis			Multivariate analysis
	Odds ratio	95%CI	P value	Adjusted odds ratio	95%CI	P value
Baseline demographic information
Age	1	1.0-1.1	0.817	1	1.0-1.1	0.142
Male sex	0.9	0.3-2.9	0.807	-	-	-
Hematological parameters change with response to dengue severity
Hematocrit	1	0.9-1.1	0.96	-	-	-
WBC count	1	1.0-1.0	0.856	-	-	-
Percentage of neutrophils	1.1	1.0-1.1	0.036a	-	-	-
Percentage of atypical lymphocytes	1	0.9-1.1	0.467	-	-	-
Platelet count	1	1.0-1.0	0.673	-	-	-
Liver status at diagnosis of DISH
Total bilirubin	1	0.9-1.1	0.789	0.8	0.5-1.3	0.347
SGPT	1	1.0-1.0	0.004b	-	-	-
INR	6.5	2.6-16.2	< 0.001c	10.4	2.6-40.5	0.001d
Albumin	0.2	0.1-0.5	0.003e	0.2	0.04-1.3	0.104
Creatinine	1.6	1.01-2.4	0.046f	1.2	0.8-1.9	0.419
MELD score	1.1	1.1-1.2	0.001g	-	-	-
Presence of liver comorbidity	1	0.1-8.2	0.983	-	-	-

^aP < 0.05.

^bP < 0.005.

^cP < 0.001.

^dP = 0.001.

^eP < 0.005.

^fP < 0.05.

^gP = 0.001. DISH: Dengue-induced severe hepatitis; WBC: White blood cell; INR: International normalized ratio; SGPT: Serum glutamate-pyruvate transaminase; MELD: Model for End-Stage Liver Disease; CI: Confidence interval.

Table 4 Summary of the clinical characteristics of dengue-induced severe hepatitis patients with acute liver failure

Number	Sex	Age	Dengue severity	Dengue complications					Treatment for ALF/HE	Duration (d)			Treatment outcome
				Sepsis	ARDS	Syst. Bleed.	Renal failure	Other		HE	ICU	Hospital	Status	Cause of death
1	F	23	DSS	No	No	Yes	Yes	No	None	1	1	3	Dead	CV failure
2	F	19	DSS	No	No	Yes	Yes	No	NAC	2	2	4	Dead	CV failure
3	M	11	DSS	Yes	No	Yes	Yes	No	None	5	21	22	Dead	Liver failure
4	M	16	DSS	No	No	Yes	Yes	DIC	SPAD NAC	4	7	26	Cured	-
5	F	21	DSS	No	Yes	Yes	Yes	DIC	Mannitol steroids	5	7	8	Dead	Bleeding complication
6	F	54	DSS	No	No	Yes	Yes	No	None	6	-	106	Cured	-
7	F	35	DSS	No	No	Yes	Yes	SICM	None	2	2	4	Dead	CV failure
8	M	16	DSS	No	No	No	No	No	None	3	3	8	Cured	-
9	M	24	DHF	Yes	Yes	Yes	Yes	DIC, HLH	NAC	10	37	78	Cured	-
10	F	17	DHF	No	No	Yes	Yes	No	SPAD NAC	4	4	11	Cured	-
11	M	18	DHF	Yes	No	Yes	Yes	DIC	NAC	10	33	40	Dead	Bleeding complication
12	M	33	DHF	Yes	No	Yes	Yes	DIC, ANP	MARS NAC	4	58	63	Dead	Uncontrolled sepsis
13	M	52	DSS	No	No	No	Yes	ANP	None	2	2	2	Dead	CV failure
14	F	14	DHF	No	No	No	Yes	No	3% NaCl	2	7	7	Cured	-
15	M	11	DSS	No	Yes	Yes	Yes	DIC	SPAD	6	6	6	Dead	CV failure
16	M	39	DHF	No	No	Yes	No	No	NAC	5	8	16	Cured	-
17	M	13	DSS	Yes	Yes	Yes	Yes	No	None	5	5	5	Dead	CV failure

F: Female; M: Male; Syst. Bleed.: Systemic bleeding; HE: Hepatic encephalopathy; ALF: Acute liver failure; CLS: Capillary leakage syndrome; ARDS: Acute respiratory distress syndrome; DHF: Dengue hemorrhagic fever; DSS: Dengue shock syndrome; WI: Within; DIC: Disseminated intravascular coagulation; CV: Cardiovascular; SICM: Stress-induced cardiomyopathy; HLH: Hemophagocytic lymphangiohistiocytosis; ANP: Acute necrotizing pancreatitis; NAC: N-acetylcysteine; SPAD: Single-pass albumin dialysis; MARS: Molecular adsorbent recirculating system.

Table 5 Factors associated with the risk of death among dengue-induced severe hepatitis patients with acute liver failure

Factors	Dengue survivors (n = 7)	Dengue nonsurvivors (n = 10)	Odd ratio of death	P value
Presence of DSS, n (%)	3 (42.9)	8 (80.0)	5.3	0.128
Concurrent extrahepatic organ failure, n (%)
Systemic bleeding	5 (71.4)	10 (100.0)	9.6	0.154
Bacterial sepsis	2 (28.6)	6 (60.0)	3.8	0.211
Renal failure	5 (71.4)	9 (90.0)	3.6	0.341
ARDS	1 (14.3)	3 (30.0)	2.6	0.461
DIC	2 (28.6)	5 (50.0)	2.5	0.382
Multiple (≥ 2) extrahepatic organ failure, n (%)	3 (42.9)	8 (80.0)	5.3	0.128
Liver-specific treatment, n (%)
Any treatment1	5 (71.4)	5 (50.0)	0.4	0.382
Intravenous NAC	4 (57.1)	4 (40.0)	0.5	0.488
Artificial liver support	2 (28.6)	2 (20.0)	0.6	0.683

¹In comparison with conservative treatment. ARDS: Acute respiratory distress syndrome; DIC: Disseminated intravascular coagulation; NAC: N-acetylcysteine; DSS: Dengue shock syndrome.