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Digestive Diseases and Sciences, Vol. 48, No. 6 (June 2003), pp. 11181123 (
C 2003)

Gastroduodenal Ulcer and Erosions Are Related

to Portal Hypertensive Gastropathy and Recent
Alcohol Intake in Cirrhotic Patients
JEAN AUROUX, MD,* DOMINIQUE LAMARQUE, MD,* FRANCOISE ROUDOT-THORAVAL, MD,
ESE
LIONEL DEFORGES, MD, MARIE THER ` CHAUMETTE, MD, JEAN PHILIPPE RICHARDET, MD,*
and JEAN CHARLES DELCHIER, MD,*

Gastroduodenal ulcers and gastroduodenal erosions are particularly frequent in cirrhotic patients,
but their precise cause is unclear. The aim of this study was to identify pathogenic factors asso-
ciated with ulcers and erosions in patients with cirrhosis. We studied 64 consecutive patients with
cirrhosis referred for gastroscopy. The severity of portal hypertensive gastropathy was graded with
an endoscopic score. H. pylori status was determined by histological examination of gastric biopsy
samples or by the [13 C] urea breath test. The daily alcohol intake within the preceding week was
recorded. The Child-Pugh score was determined. Fifteen patients had gastroduodenal ulcer and 20
had gastroduodenal erosions. Cirrhosis was related to alcohol in 44 patients and hepatitis B or C
virus in 14 patients. The portal hypertensive gastropathy was graded as severe in 12 patients and
mild in 25 patients. H. pylori infection, found in 37 patients, was not related to the gastroduode-
nal lesions. Univariate and multivariate analysis showed the links between gastroduodenal erosions
and hypertensive gastropathy and recent heavy drinking. Gastroduodenal ulcer was independently
associated only with the severity of the gastropathy. In conclusion, in these patients with cirrhosis,
the presence of gastroduodenal ulcer was significantly related to hypertensive gastropathy but not to
H. pylori infection. Recent alcohol intake favored the occurrence of gastroduodenal erosions.

KEY WORDS: cirrhosis; H. pylori; gastroduodenal ulcer; portal hypertensive gastropathy.

Gastroduodenal ulcerative lesions are more frequent in
cirrhotic patients than in the general population (1), but
the reasons are unclear. Factors suspected of playing a
role are weakness of the mucosal barrier related to liver
disease, and/or excessive exposure to agents capable of
Manuscript received September 10, 2000; revised manuscript received
December 7, 2000; accepted January 15, 2001.
From the *Service dHepatologie et de Gastroenterologie, Service
de Sante publique, Service de Bacteriologie et de Virologie,
and Departement dAnatomie Pathologique, Hopital Henri Mondor,
AP-HP, Universite Paris XII, 51 Avenue du Marechal De Lattre de
Tassigny, F-94010 Creteil. France.
Address for reprint requests: Dr. D.Lamarque, Service dHepatologie
et de Gastroenterologie, Hopital Henri Mondor, Universite Paris XII, 51
Avenue du Marechal De Lattre de Tassigny, F-94010 Creteil, France.
damaging the mucosa, such as alcohol, tobacco, acids,
and Helicobacter pylori.
The changes in the gastric mucosa induced by por-
tal hypertension lead to an endoscopic feature called hy-
pertensive gastropathy, associated with a mosaic pattern,
mucosal erythema, and fold thickening. The mucosa of
patients with hypertensive gastropathy due to alcoholic
cirrhosis is more susceptible to damaging agents such as
bile salts and alcohol, suggesting mucosal weakness (2).
Such weakness could also be related to liver failure (3)
or to the severity of the hypertensive gastropathy, which
has never been examined as a potential risk factor for ul-
cerative damage. Smoking, which correlates in the general
population with heavy drinking, is a recognized risk factor
for gastroduodenal ulcer (4). High acid secretory output,

1118 Digestive Diseases and Sciences, Vol. 48, No. 6 (June 2003)
0163-2116/03/0600-1118/0
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RISK FACTORS FOR GASTRODUODENAL UCLER AND EROSIONS IN CIRRHOTICS
which could be induced by the hypergastrinemia some-
times observed in cirrhotic patients with portal hyper-
tension, has also been suspected of playing a pathogenic
role (5, 6).
H. pylori infection is the main cause of gastroduode-
nal ulcer disease in the general population, but its role
in the onset of gastroduodenal ulcer in patients with
cirrhosis has not been clearly established (7). Different
prevalence rates have been reported, depending on the
method used to diagnose H. pylori infection (810). His-
tology is the most accurate way of demonstrating the pres-
ence of the bacterium, but the [13 C]urea breath test is
a valuable alternative method. Therefore, in this study,
H. pylori was screened for by means of histology if pos-
sible, and by the urea breath test in patients with clotting
disorders.
We prospectively assessed the importance of the follow-
ing recognized pathogenic factors in gastroduodenal ulcer
and erosions in patients with cirrhosis: severity and cause
of cirrhosis, portal hypertensive gastropathy, H. pylori in-
fection, hypergastrinemia, alcohol intake, and smoking.
Particular attention was paid to the severity of the hyper-
tensive gastropathy.
MATERIALS AND METHODS
Patients. Sixty-four consecutive patients with cirrhosis re-
ferred to the endoscopy unit of Henri Mondor Hospital, Creteil,
France, were enrolled in the study. Upper gastrointestinal en-
doscopy was routinely used as part of the assessment of portal
hypertension. The study protocol was approved by the institu-
tional ethics committee and conformed to the ethical guidelines
of the 1975 Declaration of Helsinki. Patients gave their informed
consent for biopsy sampling and the urea breath test. Patients
with previous gastric surgery (except simple suture for perfo-
ration) or who had taken nonsteroid antiinflammatory drugs,
antisecretory drugs, sucralfate, misoprostol, and antimicrobial
agents in the previous 14 days were not eligible. Upper diges-
tive tract bleeding within the last week was also an exclusion
criterion.
Cirrhosis was diagnosed by liver biopsy in all patients. The
severity of cirrhosis was assessed using the Child-Pugh classifi-
cation (11). The etiology of the cirrhosis was defined as alcoholic
if there was a daily ethanol intake of >80 g/day for at least 5 years
and as viral when HBs antigen or antibodies to hepatitis C virus
were present. Less common diseases, such as hemochromatosis
and primary biliary cirrhosis were diagnosed according to the
latest clinical criteria.
Endoscopic Examination. All patients underwent upper gas-
trointestinal endoscopy (GIF 100, Olympus) performed by ex-
perienced endoscopists. Each endoscopy was recorded and two
investigators independently assessed the recordings. Ulcerated
lesions in the duodenal or gastric wall were defined as an exca-
vated mucosal break at least 5 mm in diameter (as measured with
biopsy forceps), with a distinct crater and border, and erosions in
the stomach and duodenum were defined as superficial mucosal
breaks.
Digestive Diseases and Sciences, Vol. 48, No. 6 (June 2003)
The severity of hypertensive gastropathy was graded with a
scoring system described in a previous study (12), as follows: ab-
normalities (mosaic pattern, mucosal erythema, and fold thick-
ening) in the antrum and fundus were graded as 0, absent; 1,
localized; 2, diffuse but not circumferential; or 3, diffuse and
circumferential. The total score, from 0 to 18, corresponding to
the severity of the gastropathy, was established from the sum of
the abnormalities graded in the fundus and antrum. The size of
esophageal varices was graded from 0 to 3.
H. pylori Screening. H. pylori status was determined in all
patients by means of a rapid urease test and also by biopsy
or the [13 C]urea breath test (when biopsy was contraindicated
by clotting disorders). Three endoscopic biopsies were taken
from the antrum (3 cm from the pylorus) and from the fundus,
and H. pylori infection was diagnosed by histological examina-
tion of formalin-fixed mucosal samples stained with cresyl fast
violet.
The urea breath test was performed according to an estab-
lished protocol (13). After an overnight fast, a baseline breath
sample was collected, after which the subject was given 100 ml of
water with 1.4 g of citric acid. Five minutes later a second base-
line breath sample was collected. Then, the subject was given
100 ml of water with 75 mg of [13 C]urea, and breath samples
were collected 30 min later. The 13 C/12 C isotope ratio in the
breath samples was determined with a mass spectrometer (Op-
tima, Fisons Instruments). Patients were considered infected at
113 CO2 level of 5 per mil.
Evaluation of Other Factors Associated with
Gastroduodenal Ulcer or Erosions. The patients were
asked about their smoking and drinking during the previous
7 days. Daily alcohol intake in grams per day was graded, as
follows: 0 g/day, grade 0; 020 g/day, grade 1; 2040 g/day,
grade 2; 4060 g/day, grade 3; 6080 g/day, grade 4; and
>80 g/day, grade 5. Smoking was semiquantified into 5 grades,
as follows: 0 cigarettes/day, grade 0; 010 cigarettes/day, grade
1; 1020 cigarettes/day, grade 2; 2040 cigarettes/day, grade
3; more than 40 cigarettes/day, grade 4. The basal fasting
gastrinemia was determined.
Statistical Analysis. Comparisons between risk factors for
gastroduodenal ulcer or erosions were based on univariate anal-
ysis using Pearsons 2 test or Fishers exact test. Significant
predictive factors were entered into a multivariate logistic regres-
sion model and examined for the significance of the likelihood
ratio using a stepwise procedure with backward elimination.
RESULTS
The 64 patients who met the inclusion criteria were en-
rolled in the study over a 10-month period. There were
52 men and 12 women with a mean (SD) age of 56
(11) years (range 2775 years). The cause of cirrhosis
was alcohol in 44 patients, HCV in 10, HBV in 3, HCV
and alcohol in 2, HBV and alcohol in 1, hemochromatosis
in 1, primary biliary cirrhosis in 1, drugs in 1, and crypto-
genetic in 1. The Child-Pugh classification was as follows:
A in 19 patients, B in 21, and C in 24.
Endoscopic Findings. Gastroduodenal ulcer was di-
agnosed in 15 patients (23.4%) (8 patients with gastric ul-
cers and 7 with duodenal ulcers; 1 patient had both gastric
1119
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pp692J-ddas-467454 DDAS.cls May 9, 2003 12:58
and duodenal ulcers). Twenty patients (31.2%) had gastric
and/or duodenal erosions (18 patients with gastric ero-
sions, 1 patient with duodenal erosions, and 1 patient with
both gastric and duodenal erosions). Eight patients with
gastroduodenal ulcers had gastric or duodenal erosions;
of these, 6 patients had both gastric ulcer and gastric ero-
sions, and 1 patient had both duodenal ulcer and duodenal
erosions.
Gastroscopy identified esophageal varices in 56 patients
(87.5%), which were grade 1 in 14 patients, grade 2 in
36, and grade 3 in 6. The severity of the hypertensive
gastropathy in the antrum and fundus was scored from
0 to 6 in 25 patients, from 7 to 12 in 27 patients, and
from 13 to 18 in 12 patients. Eight patients had no gastric
abnormalities and scored 0 for this item.
H. pylori Status. Among the 47 patients who had gas-
tric biopsies, H. pylori infection was found in 31 pa-
tients (66%) by both the rapid urease test and histolog-
ical examination. The breath test, performed in the other
27 patients, was positive in 13 cases (48.1%). Whatever
the screening method, H. pylori status was positive in
37 patients (57.8%). Five of the 8 patients with duode-
nal ulcer and 5 of the 8 patients with gastric ulcer had
H. pylori infection. The prevalence of H. pylori infec-
tion did not vary according to the Child-Pugh grade (11
of 19 grade A, 13 of 21 grade B, and 13 of 24 grade C
patients).
Other Factors Studied. Daily ethanol consumption
over the previous 8 days was graded 0 in 39 patients, 1 in 4,
2 in 3, 3 in 2, 4 in 0 and 5 in 16 patients. Daily tobacco con-
sumption over the previous 8 days ranged as follows: grade
0 in 41 patients, grade 1 in 9, grade 2 in 4, grade 3 in 5,
and grade 4 in 5. The mean ( SE) plasma gastrin concen-
tration was 68 55 pmol/1iter (range: 28267 pmol/liter;
N = 64). The value was higher than 200 pmol/liter in 4
patients, only one of whom had gastroduodenal ulcer and
none had gastroduodenal erosions.
Factors Associated with Gastroduodenal Ulceration
and Erosions. Univariate analysis showed that neither
sex nor age was significantly associated with gastroduo-
denal ulceration or gastroduodenal erosions. The mean age
( SEM) of the patients with gastroduodenal ulcer (53
9 years) or erosions (55 10 years) and of those without
ulcers or erosions (56 11 years) was not significantly
different. The difference in the sex ratio (male/female) be-
tween patients with gastroduodenal ulcer (15/0) and pa-
tients without gastroduodenal ulcer (37/12) was not signif-
icant. Similarly, it was not significantly different between
the group with erosions (16/4) and the group without ero-
sions (36/8). The etiologies of cirrhosis (alcohol/others)
were not differently distributed among patients with gas-
troduodenal ulcer (12/3) or gastroduodenal erosions (16/4)
1120
AUROUX ET AL
and in those without gastroduodenal ulcer (39/10) or ero-
sions (31/13).
Links between gastroduodenal ulcer or erosions and
Child-Pugh criteria, the size of esophageal varices, the
grade of hypertensive gastropathy, H. pylori status, the
plasma gastrin concentration, and daily ethanol and to-
bacco consumption were also tested in univariate analysis
(Table 1). Five of the 8 patients with duodenal ulcer and 5
of the 8 patients with gastric ulcer (including the patient
with both types of ulcer) were infected by H. pylori.
The mean Child-Pugh score was not significantly dif-
ferent in the 8 patients with gastric ulcer (8.6 0.8) and
those without ulcers (8.3 0.9). Likewise, the score was
not influenced by the presence (8.8 0.8) or absence
(8.3 0.3) of duodenal ulcer.
The mean plasma gastrin level was not signifi-
cantly different between patients with gastroduodenal
ulcer (62 7.4 pmol/liter) or gastroduodenal erosions
(53.8 3.8 pmol/liter) and patients without ulcers (67
13 pmol/liter) or erosions (71.8 9.2 pmol/liter).
In multivariate analysis, a hypertensive gastropathy
score higher than 12, and current daily consumption al-
cohol about 40 g/day were the only factors independently
related to erosions [odds.ratio (OR) = 1.2 confidence in-
terval (CI) = 1.112.2, P < 0.006; and OR = 3.7, CI =
1.112.3, P < 0.028, respectively], while a hypertensive
gastropathy score higher than 12 was the only factor in-
dependently related to gastroduodenal ulcer (OR = 1.8,
CI = 1.11.4, P < 0.004).
DISCUSSION
We observed a high prevalence of gastroduodenal ulcer
(23.4%) in these patients with cirrhosis. This is in keeping
with the significantly higher incidence of gastroduodenal
ulcer in cirrhotic patients as compared to controls (1, 79,
14). The prevalence of duodenal ulcer (12.5%) and gastric
ulcer (12.5%) was identical, whereas most reports show
a slightly higher prevalence of duodenal ulcer (1126%)
than of gastric ulcer (9.616%) (7, 8, 14). The prevalence
of gastroduodenal erosions in this study (31.2%) was very
close to that observed in a previous study (29.6%) (15).
We examined the respective roles of H. pylori, portal
hypertension, liver failure, smoking and alcohol consump-
tion, and hypergastrinemia in gastroduodenal ulcer and
erosions. We found no link with H. pylori, confirming pre-
vious reports (7, 8, 16, 17). The prevalence of H. pylori
infection in this study (57.8%) was in keeping with that
observed in other studies, in which the prevalence ranged
from 45 to 75% (9, 10, 14). However, most of these latter
studies used serological tests for H. pylori, whereas we de-
tected the bacterium in the mucosa by means of histology
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RISK FACTORS FOR GASTRODUODENAL UCLER AND EROSIONS IN CIRRHOTICS

TABLE 1. RELATIONSHIP BETWEEN GASTRODUODENAL ULCER OR EROSIONS AND CIRRHOSIS SEVERITY, HYPERTENSIVE
GASTROPATHY, H. pylori STATUS, AND ALCOHOL /TOBACCO CONSUMPTION (UNIVARIATE ANALYSIS)

Gastroduodenal No gastroduodenal Erosions No erosion

ulcer (N = 15) ulcer (N = 49) (N = 20) (N = 44)

Child-Pugh group
A 3 (20%) 16 (33%) 4 (20%) 15 (34%)
B 6 (40%) 15 (31%) 10 (50%) 11 (25%)
C 6 (40%) 18 (37%) 6 (30%) 18 (41%)
Esophageal varices
Grade 01 4 (27%) 18 (37%) 6 (30%) 16 (36%)
Grade 23 11 (73%) 31 (63%) 14 (70%) 28 (64%)
Hypertensive gastropathy
Grade 012 8 (53%) 44 (90%) 12 (60%) 40 (91%)
Grade 1318 7 (47%)* 5 (10%) 8 (40%) 4 (9%)
H. pylori infection status
Negative 6 (40%) 21 (43%) 12 (60%) 15 (34%)
Positive 9 (60%) 28 (57%) 8 (40%) 29 (66%)
Daily alcohol intake (g/day)
<40 6 (40%) 39 (80%) 13 (65%) 33 (75%)
40 8 (60%) 10 (20%) 7 (35%) 11 (25%)
Tobacco consumption (cigarettes/day)
0 8 (53%) 33 (67%) 11 (55%) 30 (68%)
<20 3 (20%) 10 (21%) 6 (30%) 7 (16%)
>20 4 (27%) 6 (12%) 3 (15%) 7 (16%)
*P < 0.01 compared to the group without gastroduodenal ulcer.
P < 0.05 compared to the group without gastroduodenal ulcer.
P < 0.02 compared to the group without gastroduodenal erosion.

or the urea breath test. In the only published study us-
ing both these tests, the prevalence of H. pylori infection
was 45.5% among cirrhotic patients with a mean age of
57 years, which is very similar to the mean age of our
patients (56 years) (18).
In a study by Schmulson et al, the prevalence of
H. pylori was higher in child-Pugh class A than in other
classes. In contrast, we found no link between H. pylori
status and the Child-Pugh class. It has been suggested that
mucosal congestion related to hypertensive gastropathy
could contribute to reducing the density of H. pylori (19).
Moreover, the repeated courses of antimicrobials admin-
istered to patients with severe cirrhosis may also reduce
bacterial density in stomach. This is why patients who
had recently taken antimicrobial drugs were not eligible
for our study.
H. pylori infection was found in 62.5% of our cirrhotic
patients with duodenal ulcer, a prevalence in keeping with
that found in other studies (4083%) (7, 8, 17), but much
lower than the prevalence commonly reported in noncir-
rhotic duodenal ulcer patients (20). This suggests that gas-
tric infection by H. pylori does not play the same role in
the pathogenesis of duodenal ulcer in cirrhotic patients as
in the general population.
The role of portal hypertension in the pathogenesis of
ulcers has previously been raised. However, neither the
presence nor the size of esophageal varices correlated
with gastroduodenal ulcer in our study, in keeping with
previous results (7, 8). Gastroduodenal ulcer and erosions
in cirrhotic patients could be related to the changes in-
duced in the gastric mucosa by hypertensive gastropathy
(7). Experimental studies in animals with portal hyperten-
sion have shown an increased susceptibility of the gastric
mucosa to damaging agents, which cause extensive ulcer-
ations (2). We found a close link between a high congestive
gastropathy score (>12) and the presence of gastroduo-
denal ulcer or erosions. The congestive gastropathy was
semiquantified by using a previously described score (12)
that integrates mucosal features such as fold thickness,
erythema, and a mosaic pattern. A relationship between
congestive gastropathy and gastroduodenal ulcer has been
reported in H. pylori-free patients with cirrhosis (8), but
the congestive gastropathy was not graded and no the link
with the severity could therefore be found.
The pathogenic mechanism underlying ulcerations in
hypertensive gastropathy is unclear. The hepatorenal shunt
associated with portal hypertension may reduce gastric
mucosal blood flow and the production of vasodilatory
factors such as prostaglandins (21, 22). These factors do
not seem to be linked to the severity of liver failure. Like
these experimental reports and previous clinical studies,
our findings support a lack of any such relationship, as the
prevalence of gastroduodenal ulcer was not more frequent
in patients with high Child-Pugh scores (7, 15). Similarly,
the prevalence of erosions was independent of the Child-
Pugh score, which was not significantly different between

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patients with gastroduodenal erosions and patients with-
out erosions. A previous study (15) suggested that de-
compensated cirrhosis could be a risk factor for the devel-
opment of gastroduodenal erosions, but the difference in
the rate of gastroduodenal erosions (48% in Child C pa-
tients and 21% in Child A patients) did not reach statistical
significance.
Although related to impaired hydrochloric acid secre-
tion in most cirrhotic patients, hypergastrinemia could be
a primary event, itself stimulating acid secretion and in-
ducing gastroduodenal ulcer in some patients (5, 6). In
our study, increased serum gastrin concentrations could
not be incriminated as a risk factor, as levels did not ex-
ceed the normal range in most patients (93.8%). Only
one of the 4 patients who had gastrinemia values above
200 pmol/liter had a duodenal ulcer. The other three pa-
tients had no mucosal lesions in the stomach or duode-
num. These results are in keeping with those of a re-
cent study showing similar serum gastrin concentrations in
28 patients with cirrhosis and 275 controls (23).
Recent daily alcohol intake before endoscopy was in-
dependently associated with the prevalence of gastroduo-
denal ulcer or erosion in these cirrhotic patients. No such
link has been described in noncirrhotic patients, and al-
cohol intake exceeding 30 g/day has not been linked to
a higher risk of duodenal ulcer in the general population
(2426). The link between alcohol intake and ulcerative
damage in cirrhosis suggests that cirrhosis may increase
the susceptibility of the gastric mucosa to ethanol toxicity.
This susceptibility could be mediated by the lack of a re-
active hyperemic response to topical ethanol application
recently described in a rat model (27). In contrast, chronic
alcohol intake does not seem to play a role in the ulcero-
genic process, as the prevalence of gastroduodenal ulcer
was not different between patients with cirrhosis due to
alcohol and those with cirrhosis due to other causes, con-
firming the results of previous studies (18, 28).
We did not find an increased risk of gastroduodenal ul-
cer in smokers. A link between cigarette smoking and gas-
troduodenal ulceration has been suggested on theoretical
and epidemiological grounds (4, 29), but this risk factor
has not been confirmed in cirrhotic patients (10).
In conclusion, risk factors for gastroduodenal ulcer in
cirrhotic patients seem to be different from those gener-
ally incriminated in the general population. The increased
risk of gastroduodenal ulcer in cirrhotic patients was not
related to H. pylori infection in this study. In contrast, two
factors were found to increase the risk of gastroduodenal
ulcer in this cirrhotic population: high-grade hypertensive
gastropathy and recent alcohol consumption. These find-
ings suggest that H. pylori eradication is not sufficient to
treat gastroduodenal ulcers in cirrhotic patients. The po-
1122
AUROUX ET AL
tential value of long-term antisecretory treatment should
now be assessed in such patients.
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