Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care

Table 1 Baseline characteristics of study patients

Parameter	n (%)
Age (yr)	57 (IQR 50–65)
Male	133 (71)
Current smoker	70 (37)
Co morbidities
IHD	16 (9)
DM	64 (34)
CCF	16 (9)
Previous CVA	15 (8)
COPD	14 (7)
Non-HCC malignancy	20 (11)
CKD	39 (21)
Ascites	138 (73)
Aetiology of cirrhosis
Alcohol	117 (62)
HBV	6 (3)
HCV	59 (31)
NASH	37 (20)
PSC	6 (3)
AIH	4 (2)
PBC	1 (1)
Other	11 (6)
Child Pugh score	11 (IQR 9-12)
CPA	3 (2)
CPB	39 (21)
CPC	120 (64)
Unknown	26 (14)
MELD	25 (IQR 18-31)
Hepatic encephalopathy
Grade 1	22 (5)
Grade 2	93 (23)
Grade 3	38 (57)
Grade 4	9 (14)
Unknown grade	26
Previous episode of encephalopathy	75
Median duration of encephalopathy (d)	7 (IQR 2-9)

Continuous variables are presented as median (interquartile range). IHD: Ischemic heart disease; DM: Diabetes mellitus; CCF: Congestive cardiac failure; CVA: Cerebrovascular event; COPD: Chronic obstructive pulmonary disease; HCC: Hepatocellular cancer; CKD: Chronic kidney disease; HCV: Hepatitis C; HBV: Hepatitis B; NASH: Non-alcoholic steatohepatitis; PSC: Primary sclerosing cholangitis; AIH: Autoimmune hepatitis; PBC: Primary biliary cirrhosis; CPA: Child's Pugh A; CPB: Childs Pugh B; CPC: Childs Pugh C; MELD: Model for end-stage liver disease.

Table 2 Baseline laboratory parameters

Parameters	mean ± SD
Haemoglobin (g/L)	90 ± 20
Platelet (× 109/L)	86.1 ± 64
White cell count (× 109/L )	8 ± 6
Bilirubin (µmol/L)	151 ± 168
Albumin (g/L)	25 ± 7
ALT (U/L)	135 ± 468
ALP (U/L)	166 ± 106
GGT (U/L)	154 ± 262
INR	2.1 ± 1.0
Urea (mmol/L)	11 ± 7
Creatinine (micromol/L)	161 ± 138
Sodium (mmol/L)	133 ± 7
Potassium (mmol/L)	4.5 ± 1.0

ALT: Alanine transaminase; ALP: Alkaline Phosphatase; GGT: Gamma glutamyl transferase; INR: international normalised ratio.

Table 3 Precipitating factors for hepatic encephalopathy (alone or in combination with other factors)

Precipitating factors	n (%)
Infection including SBP	81 (43)
Gastrointestinal bleeding	31 (16)
Constipation (opiate-induced)	10 (5)
Constipation (not opiate induced)	25 (13)
Benzodiazepine use	10 (5)
Noncompliance to regular medications	29 (15)
Electrolyte imbalance	27 (14)
Other	24 (13)
Unknown	15 (8)

SBP: Spontaneous bacterial peritonitis.

Table 4 Hazard ratio for the different variables investigated by univariate analysis and multivariate analysis as possible prognostic factors in 188 cirrhotic patients presenting with hepatic encephalopathy and commenced on rifaximin

Variable	Univariate hazard ratio using cox regression (95%CI)1	Multivariate hazard ratio (95%CI)1
Age	1.014 (0.99, 1.03)
Sex (male vs female)	1.087 (0.75, 1.58)
Aetiology of cirrhosis2
HBV infection	0.76 (0.28, 2.05)
HCV infection	0.62 (0.42, 0.91)a
Alcohol	0.92 (0.65, 1.30)
Precipitating factors2
Gastrointestinal bleed	0.75 (0.46, 1.22)
Infection	1.49 (1.03, 2.15)a
Diuretic therapy	1.47 (0.94, 2.32)
Constipation	1.19 (0.73, 1.95)
Ascites at the time of HE2	1.11 (0.77, 1.59)
Maximal grade of HE (grade 3 and 4 vs grade 1 and 2)	0.80 (0.53, 1.21)
Serum values3
Bilirubin	1.001 (1, 1.002)a
ALT	1 (0.99, 1.003)
GGT	1 (1, 1)
Albumin	0.97 (0.95, 1.002)
Urea	1.05 (1.02, 1.09)a
Creatinine	1.001 (1, 1.002)a
Sodium	0.99 (0 .97, 1.03)
Potassium	1.16 (0.96, 1.40)
INR	1.5 (1.21, 1.85)a	1.27 (1.04, 1.54)a
Hb	0.98 (0.97, 1.01)
WCC	1.06 (1.02, 1.10)a
Plt	1.00 (0.99, 1.01)
Child Pugh Score (C vs A/B)	1.57 ( 1.02, 2.41)a
MELD	1.03 (1.01, 1.06)a
MELD (≥ 15 vs ≤ 15)	2.41 ( 1.20. 4.85)a	2.17 (1.07, 4.43)a

¹In brackets: 95% confidence interval.

²Presence vs absence.

³Hazard ratio per unit increase.

^aP ≤ 0.05. HE: Hepatic encephalopathy; HCV: Hepatitis C; HBV: Hepatitis B; ALT: Alanine transaminase; GGT: Gamma glutamyl transferase; INR: international normalised ratio; Hb: Haemoglobin; WCC: White cell count; Plt: Platelet count; MELD: Model for end-stage liver disease.