Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients

Table 1 Grade of hepatic encephalopathy in proton pump inhibitor users versus nonusers

Grade of HE	PPI user	PPI nonuser
	n = 75	n = 28
Grade 1	15 (20.0)	11 (39.3)
Grade 2	32 (46.6)	13 (46.4)
Grade 3	18 (24.0)	4 (14.3)
Grade 4	10 (13.4)	0 (0)

n (%), Grade of hepatic encephalopathy (HE) is defined by the West Haven Criteria Severity Scale for HE: Grade I (mild confusion, disordered sleep), II (lethargy moderate confusion), III (marked confusion, incoherent speech), IV (coma). HE: Hepatic encephalopathy; PPI: Proton pump inhibitor.

Table 2 Participant characteristics

Variables	Total, n = 103	PPI user, n = 75	PPI nonuser, n = 28	P value
Age, yr, Mean ± SD	58.3 (10.8)	59.6 (10.6)	55.3 (10.7)	0.044a
Sex, male, n (%)	71 (58.7)	54 (63.5)	17 (47.2)	0.143
On lactulose, n (%)	92 (76)	63 (74.1)	29 (80)	0.599
Bleeding in last 12 mo, n (%)	39 (32.2)	26 (30.6)	13 (36.1)	0.703
Infection, n (%)
Clostridium difficile colitis	5 (4.1)	5 (5.9)	0 (0)	0.324
Pneumonia	11 (9.1)	10 (11.8)	1 (2.8)	0.220
Spontaneous bacterial peritonitis	9 (7.4)	5 (5.9)	4 (11.1)	0.533
Serum ammonia level, Mean ± SD	61.1 (67.2)	67.8 (67.8)	45.5 (64.2)	0.095
Grade of hepatic encephalopathy, Mean ± SD	2.1 (0.9)	2.3 (0.9)	1.7 (0.7)	0.001b
MELD score, Mean ± SD	19.9 (7.2)	19.7 (7.4)	20.3 (6.7)	0.687
Length of stay in d, Mean ± SD	8.5 (7.0)	8.3 (7.9)	6.5 (3.7)	0.046a
Required ICU, n (%)	33 (27.3)	27 (31.8)	6 (16.7)	0.138
Expired, n (%)	11 (9.1)	10 (11.8)	1 (2.8)	0.220

^aP < 0.05,

^bP < 0.01. MELD: Model for end-stage liver disease; ICU: Intensive care unit.

Table 3 Linear regression models, grade of hepatic encephalopathy

Variables	Β ± SE	P value
Model 1, demographic variables
Age	-0.001 ± 0.001	0.871
Sex	0.062 ± 0.167	0.710
PPI use	0.607 ± 0.180	0.001b
Model 2, medical comorbidities
Age	0.002 ± 0.008	0.787
Sex	0.043 ± 0.166	0.797
MELD Score	0.020 ± 0.011	0.079
PPI Use	0.607 ± 0.179	< 0.001b
Model 3, other medications
Age	0.004 ± 0.008	0.647
Sex	0.033 ± 0.164	0.839
MELD Score	0.024 ± 0.011	0.041a
Lactulose	0.324 ± 0.189	0.089
PPI use	0.625 ± 0.178	< 0.001b

^aP < 0.05,

^bP < 0.01. B ± SE: beta ± standard error. MELD: Model for end-stage liver disease; PPI: Proton pump inhibitor.