55 / 105
E
fficacy
of
lactulose
in
the
prophylaxis
of
hepatic
encephalopathy
in
cirrhotic
patients
presenting
gastrointestinal
bleeding
R
ev
A
ssoc
M
ed
B
ras
2016; 62(3):243-247
245
untreated group (3
vs.
7%, 95CI -0.12 to 0.06; p=0.48;
I
2
=40%), according to Figure 1.
Adverse effects of lactulose
The main adverse effects related to the use of lactulose
were diarrhea (5%) and bloating (2.5%). Two patients (1%)
needed to interrupt the intake of lactulose due to side ef-
fects. There were no significant adverse effects such as sig-
nificant abdominal pain, dehydration and electrolyte dis-
turbances during the study periods.
D
iscussion
The prognosis of a cirrhotic patient worsens quickly af-
ter hepatic encephalopathy develops. The estimated sur-
vival rate is 50% in one year, and 25% in three years after
an episode of HE.
10,11
It is known that hepatic encephalopathy is caused by
reversible factors in over 80% of patients. These factors
include gastrointestinal bleeding, bacterial infection, in-
testinal obstruction, electrolyte disturbances, protein
overload and the use of sedatives and tranquilizers. Thus,
identifying and correcting reversible precipitating factors
before deterioration of hepatocellular function may be
beneficial to prevent and treat most episodes of hepatic
encephalopathy.
10-12
Most therapies for HE are aimed at reducing the ni-
trogen load in the intestinal lumen, an approach that is
consistent with the hypothesis that this disorder results
from the accumulation of neurotoxins derived from the
intestine in patients with hepatic impairment and por-
tosystemic shunts.
13
Non-absorbable disaccharides have been used for de-
cades and are considered first-line therapy in the man-
agement of HE, although there is no evidence in compar-
ative studies that actually proves its benefits in a consistent
manner.
4,5
They act by reducing the production and ab-
sorption of ammonia in the intestinal lumen. Acidifica-
tion of the contents of the colon due to metabolism of
ammonia into acetic acid and lactic acid creates a harsh
environment for the survival of intestinal bacteria in-
volved in ammonia production, and facilitates the con-
version of NH3 into NH4 (non-absorbable). Moreover,
its cathartic effect causes increased fecal excretion of ni-
trogenous compounds.
14
TABLE 2
Demographic data referring to the primary studies.
Sharma P, 2011
Wen J, 2013
Lactulose (n=35)
Control (n=35)
Lactulose (n=65)
Control (n=65)
Age (years)
41.6±12.9
37.2±16.0
53.0±13.3
50.4±10.2
Gender
Female
5 (14%)
7 (20%)
20 (30.8%)
18 (27.7%)
Male
30 (86%)
28 (80%)
45 (69.2%)
47 (72.3%)
Hemoglobin (mg/dL)
8.4±1.5
9.3±2.3
8.6±2.1
8.6±1.9
Albumin (g/L)
2.8±0.5
3.0±0.6
3.3±0.6
3.2±0.7
Creatinine (mg/dL)
1.1±0.3
0.9±0.3
1.6±0.1
1.6±0.1
Serum potassium (mmol/L)
4.1±0.6
4.2±0.4
4.3±0.5
4.2±0.4
Bilirubin (mg/dL)
2.0 (0.5-8.6)
2.1 (0.8-6.8)
1.9 (0.5-10.5)
1.5 (0.4-9.8)
INR
1.9±0.5
1.9±0.3
-
-
PAT
-
-
16.9 (12-28.5)
17.0 (12.8-29.2)
AST (IU/L)
43 (17-250)
50 (25-180)
32 (14-423)
40 (17-468)
ALT (IU/L)
30 (15-198)
32 (11-150)
33.5 (12-270)
39.3 (13-287)
Child-Pugh Score
9.6±1.4
9.6±1.5
6 (4-12)
6 (4-12)
Source of bleeding
Varicose
35
35
43
42
Non-varicose
-
-
22
23
Etiology of cirrhosis
Alcoholic
19
14
5
7
HBV
9
11
44
42
HCV
3
3
6
4
Other
4
7
10
12
INR: international normalized ratio; PAT: prothrombin activation time; ALT: alanine aminotransferase; AST: aspartate aminotransferase; HBV: hepatitis B virus; HCV: hepatitis C virus.