Evaluation of mannitol effect in patients with acute hepatic failure and acute-on-chronic liver failure using conventional MRI, diffusion tensor imaging and in-vivo proton MR spectroscopy

Table 1 Clinical profile of acute liver failure patients

Case	Age/Sex	Etiology	Grade of HE	Jaundice-HE interval (d)	HE duration at presentation (d)	Clinical features of raised ICP
						DP	HT	B	PC	NH
1	24/M	Hepatitis E	4	7	2	+	+	-	-	+
2	14/M	Hepatitis B	4	8	2	+	+	-	+	+
3	24/F	Hepatitis B	4	23	2	+	+	+	+	+
4	46/F	Hepatitis E	4	2	2	+	+	+	+	+
5	25/F	Hepatitis E	3	2	1	+	+	-	-	-

HE: Hepatic encephalopathy; DP: Decerebrate posture; HT: Hypertension; B: Bradycardia; PC: Pupillary changes; NH: Neurogenic hyperventilation.

Table 2 Biochemical profile of acute liver failure patients

Case	Serum bilirubin (mg/dL)	ALT (U/L)	AST (U/L)	ALP (U/L)	INR	Serum sodium (mmol/L)	Serum potassium (mmol/L)	Serum creatinine (mg/dL)	Blood sugar (mg/dL, range)	Blood ammonia (&mgr;mol/dL)
1	13.3	242	349	134	1.8	142	3.8	1.2	110-186
2	26.4	1020	920	120	8.2	146	4.7	1.2	130-194	438
3	28.6	206	156	140	6.8	140	4.9	0.6	98-178	150
4	15.3	1688	276	210	5.5	145	4.3	0.6	130-188	265
5	21.5	232	142	146	2.8	143	3.6	0.4	88-176	182

ALT: Alanine transaminase; AST: Aspartate transaminase; ALP: Alkaline phosphatase; INR: International normalized ratio.

Table 3 Clinical profile of acute-on-chronic liver failure patients

Case	Age/Sex	Etiology		Grade of HE	Jaundice-HE interval (d)	HE duration at presentation (d)	Clinical features of raised ICP
		Acute	Chronic				DP	HT	B	PC	NH
1	48/M	Hepatitis E	Cryptogenic	3	17	2	+	+	-	-	+
2	48/M	Hepatitis E	Chronic Hepatitis B	4	15	3	+	+	-	+	+
3	24/F	Hepatitis E	Autoimmune	3	22	1	+	-	-	-	+
4	45/F	Hepatitis E	Chronic Hepatitis C	3	13	2	+	+	-	+	+
5	28/F	Hepatitis E	Chronic Hepatitis B	3	7	2	+	+	-	-	+

HE: Hepatic encephalopathy; DP: Decerebrate posture; HT: Hypertension; B: Bradycardia; PC: Pupillary changes; NH: Neurogenic hyperventilation.

Table 4 Biochemical profile of acute-on-chronic liver failure patients

Case	Serum bilirubin (mg/dL)	ALT (U/L)	AST (U/L)	SAP (U/L)	INR	Serum sodium (mmol/L)	Serum potassium (mmol/L)	Serum creatinine (mg/dL)	Blood sugar (mg/dL, range)	Blood ammonia (&mgr;mole/dL)	Child score	MELD score
1	18.8	346	274	148	2.6	143	3.7	1.2	130-194	180	12/15	30
2	17.2	254	142	165	2.4	144	4.9	0.9	98-210	280	13/15	29
3	25.7	636	524	164	3.7	136	4.5	0.5	98-166	261	13/15	33
4	25.1	240	320	97	3.9	145	3.9	0.9	108-210	310	14/15	34
5	10.2	279	151	79	2.25	137	4.3	0.8	89-189	210	13/15	24

ALT: Alanine transaminase; AST: Aspartate transaminase; SAP: Serum alkaline phosphatase; INR: International normalized ratio; MELD: Modified end stage liver disease.

Table 5 Peak integrals relative to those of creatine (mean ± SD) in right parietal white and gray matter in healthy controls, acute liver failure (ALF) patients and acute-on-chronic liver failure (ACLF) patients before the intravenous infusion of mannitol (pre-mannitol study) and after receiving mannitol (post-mannitol study)

Metabolites	Study
	Control (n = 5)			ALF patient (n = 5)			ACLF patient (n = 5)
	Pre-mannitol	Post-mannitol	P	Pre-mannitol	Post-mannitol	P	Pre-mannitol	Post-mannitol	P
NAA/Cr	1.25 ± 0.16	1.23 ± 0.17	0.92	1.20 ± 0.13	1.27 ± 0.32	0.75	0.90 ± 0.35	0.58 ± 0.29	0.18
Cho/Cr	0.24 ± 0.06	0.24 ± 0.08	0.75	0.18 ± 0.09	0.16 ± 0.07	0.47	0.20 ± 0.05	0.20 ± 0.03	0.75
Gln/Cr	1.44 ± 1.06	1.18 ± 0.94	0.35	3.04 ± 1.32	2.52 ± 1.56	0.25	1.44 ± 0.30	2.42 ± 1.44	0.60
Glx/Cr	2.84 ± 0.98	2.70 ± 1.21	0.60	4.46 ± 1.48	4.38 ± 1.61	0.92	2.85 ± 0.70	3.85 ± 2.13	0.35
mI/Cr	0.57 ± 0.48	0.49 ± 0.34	0.92	0.56 ± 0.15	0.47 ± 0.16	0.18	0.41 ± 0.17	0.89 ± 1.14	0.81

Cr: Creatine; NAA: N-acetylaspartate; Cho: Choline; Gln: Glutamine; Glx: Glutamine/glutamate; mI: Myoinositol.

Table 6 Summary of fractional anisotropy values (mean ± SD) from different white and gray matter regions in controls, patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) before the intravenous infusion of mannitol (pre-mannitol study) and after receiving mannitol (post-mannitol study)

Region	Study
	Control (n = 5)			ALF patient (n = 5)			ACLF patient (n = 5)
	Pre-mannitol	Post-mannitol	P	Pre-mannitol	Post-mannitol	P	Pre-mannitol	Post-mannitol	P
ALIC	0.36 ± 0.05	0.37 ± 0.04	0.60	0.30 ± 0.03	0.30 ± 0.02	0.47	0.32 ± 0.02	0.33 ± 0.02	0.56
PLIC	0.49 ± 0.05	0.48 ± 0.05	0.60	0.33 ± 0.02	0.34 ± 0.01	0.12	0.45 ± 0.03	0.40 ± 0.03	0.08
CN	0.11 ± 0.00	0.11 ± 0.00	0.47	0.09 ± 0.01	0.09 ± 0.01	0.60	0.08 ± 0.01	0.09 ± 0.01	0.56
P	0.09 ± 0.01	0.09 ± 0.01	0.92	0.06 ± 0.01	0.07 ± 0.01	0.92	0.06 ± 0.02	0.08 ± 0.01	0.15
TH	0.15 ± 0.01	0.14 ± 0.01	0.12	0.12 ± 0.00	0.12 ± 0.01	0.92	0.14 ± 0.01	0.15 ± 0.03	0.77
FWM	0.31 ± 0.03	0.30 ± 0.03	0.92	0.30 ± 0.03	0.32 ± 0.07	0.92	0.32 ± 0.04	0.36 ± 0.07	0.56
OWM	0.38 ± 0.06	0.38 ± 0.07	0.92	0.38 ± 0.04	0.37 ± 0.05	0.92	0.35 ± 0.04	0.31 ± 0.02	0.15
CC	0.53 ± 0.04	0.54 ± 0.06	0.92	0.44 ± 0.06	0.45 ± 0.02	0.35	0.50 ± 0.04	0.51 ± 0.05	0.77
Cingulum	0.36 ± 0.03	0.37 ± 0.04	0.75	0.44 ± 0.07	0.41 ± 0.03	0.25	0.38 ± 0.03	0.36 ± 0.03	0.56
Frontal cortex	0.12 ± 0.01	0.11 ± 0.00	0.47	0.12 ± 0.04	0.12 ± 0.04	0.60	0.14 ± 0.02	0.11 ± 0.02	0.08
Parietal cortex	0.12 ± 0.01	0.12 ± 0.01	0.75	0.11 ± 0.01	0.10 ± 0.01	0.75	0.14 ± 0.01	0.11 ± 0.03	0.39
Occipital cortex	0.11 ± 0.02	0.12 ± 0.03	0.47	0.14 ± 0.05	0.10 ± 0.03	0.25	0.10 ± 0.05	0.13 ± 0.03	0.39

ALIC: Anterior limb of internal capsule; PLIC: Posterior limb of internal capsule; CN: Caudate nuclei; P: Putamen; TH: Thalamus; FWM: Frontal white matter; OWM: Occipital white matter; CC: Corpus callosum.

Table 7 Summary of mean diffusivity values (mean ± SD) in units of 10^-3 mm²/s from different white and gray matter regions in controls, patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) before the intravenous infusion of mannitol (pre-mannitol study) and after receiving mannitol (post-mannitol study)

Region	Study
	Control (n = 5)			ALF patient (n = 5)			ACLF patient (n = 5)
	Pre-mannitol	Post-mannitol	P	Pre-mannitol	Post-mannitol	P	Pre-mannitol	Post-mannitol	P
ALIC	0.76 ± 0.07	0.76 ± 0.05	0.60	0.68 ± 0.02	0.68 ± 0.02	0.75	0.72 ± 0.02	0.71 ± 0.08	0.56
PLIC	0.74 ± 0.06	0.75 ± 0.05	0.75	0.67 ± 0.03	0.67 ± 0.02	0.92	0.65 ± 0.03	0.65 ± 0.04	0.77
CN	0.73 ± 0.02	0.74 ± 0.02	0.75	0.68 ± 0.01	0.69 ± 0.02	0.92	0.69 ± 0.02	0.69 ± 0.09	0.25
P	0.69 ± 0.01	0.70 ± 0.06	0.25	0.64 ± 0.03	0.63 ± 0.01	0.47	0.69 ± 0.02	0.69 ± 0.06	0.39
TH	0.72 ± 0.03	0.71 ± 0.03	0.92	0.66 ± 0.02	0.66 ± 0.04	0.92	0.71 ± 0.02	0.74 ± 0.05	0.56
FWM	0.77 ± 0.06	0.76 ± 0.07	0.75	0.67 ± 0.01	0.66 ± 0.05	0.92	0.65 ± 0.02	0.66 ± 0.13	0.25
OWM	0.76 ± 0.05	0.76 ± 0.07	0.92	0.66 ± 0.03	0.66 ± 0.05	0.75	0.76 ± 0.11	0.68 ± 0.05	0.56
CC	0.74 ± 0.07	0.74 ± 0.07	0.92	0.74 ± 0.09	0.74 ± 0.08	0.92	0.77 ± 0.09	0.77 ± 0.09	0.77
Cingulum	0.72 ± 0.05	0.72 ± 0.09	0.75	0.72 ± 0.10	0.72 ± 0.04	0.75	0.73 ± 0.03	0.70 ± 0.06	0.56
Frontal cortex	0.69 ± 0.07	0.69 ± 0.04	0.92	0.68 ± 0.04	0.68 ± 0.05	0.92	0.65 ± 0.05	0.70 ± 0.03	0.08
Parietal cortex	0.68 ± 0.06	0.68 ± 0.05	0.92	0.68 ± 0.01	0.68 ± 0.03	0.47	0.69 ± 0.04	0.63 ± 0.04	0.08
Occipital cortex	0.67 ± 0.07	0.67 ± 0.06	0.92	0.66 ± 0.02	0.66 ± 0.05	0.92	0.69 ± 0.06	0.62 ± 0.03	0.15

ALIC: Anterior limb of internal capsule; PLIC: Posterior limb of internal capsule; CN: Caudate nuclei; P: Putamen; TH: Thalamus; FWM: Frontal white matter; OWM: Occipital white matter; CC: Corpus callosum.

Table 8 Change in brain volume and cerebrospinal fluid (CSF) volume values (mean ± SD) in units of cubic centimeter from different white and gray matter regions in controls, patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) before the intravenous infusion of mannitol (pre-mannitol study) and after receiving mannitol (post-mannitol study)

Volume	Study
	Control (n = 5)			ALF Patient (n = 5)			ACLF Patient (n = 5)
	Pre-mannitol	Post-mannitol	P	Pre-mannitol	Post-mannitol	P	Pre-mannitol	Post-mannitol	P
Brain volume	1303.47 ± 54.95	1308.88 ± 64.95	0.75	1130.76 ± 86.73	1162.39 ± 77.75	0.47	1096.85 ± 79.55	1076.90 ± 71.63	0.60
CSF volume	84.05 ± 4.88	85.10 ± 6.46	0.60	73.77 ± 19.72	73.27 ± 19.53	0.47	76.77 ± 18.68	83.84 ± 22.09	0.12