Journal of Hepatology 1995; 22: 633-l
Printed in Denmark AN rights reserved
Peptic ulcer and its course in cirrhosis: an endoscopic and clinical
prospective study
Sebastino Siringo, Andrew K. Burroughs’, Luigi Bolondi, Anna Muia, Giulio Di Febo, Mario Miglioli,
Giancarlo Cavalli and Luigi Barbara
Istituto di Clinica Medica e Gastroenterologia, Universitci di Bologna, Bologna, Italy and ‘Hepato-Biliary
Royal Free Hospital and School of Medicine, London, UK
The epidemiological and clinical characteristics of
peptic ulcer were studied in 324 of 368 consecutive
patients with cirrhosis of the liver during a mean
period of 1.2 (20.61) years. Peptic ulcer prevalence
rates in patients with cirrhosis were as follows: point
prevalence 11.7%, period prevalence Xl%, and life-
time prevalence 24.2%. The annual incidence rate ob-
served in 140 patients with cirrhosis undergoing endo-
scopic follow up was 4.3%.
Ulcers were asymptomatic in more than 70% of pa-
tients. The peptic ulcer complication rate at entry
was 20% in the whole group and 40% in those who
had not a previous diagnosis of peptic ulcer when
admitted to the study. Peptic ulcer was more fre-
quent among HBsAg+ cirrhotics (p=O.O5). Patients
with more severely decompensated cirrhosis also had
M ANY STUDIES show that there is an increased fre-
quency of peptic ulcer in patients with cirrhosis
(l-7). However, little information is available about the
relationship of ulceration to the degree of liver impair-
ment, the clinical features of the ulcers, the response
to therapy, the risk of complications, and the need for
endoscopic follow up.
Our own previous uncontrolled experience led us to
suspect that in patients with cirrhosis, particularly in
those with impaired liver function, peptic ulcer was not
only more frequent, but usually occurred without con-
comitant abdominal pain and was often complicated
by bleeding. Moreover, the response to standard H2
antagonist therapy seemed poor, both in terms of heal-
ing and in preventing recurrences.
Received 20 February 1994
Correspondence: Dr S. Siringo, Istituto di Clinica Medica
e Gastroenterologia, Policlinico S. Orsola, Via Massarenti
No 9, 40138 Bologna, Italy.
Copyright 0 Journal of Hepardogy 1995
Journalof Hepatology
ISSN 0168-8278
and Liver Transplantation Unit,
a higher frequency of asymptomatic ulcers (p=O.O4),
gastric ulcers (p=O.Ol) and asymptomatic gastric ul-
cers (p=O.O05). After diagnosis, during endoscopic
follow up, gastric ulcer in patients with cirrhosis
tended to heal slowly and recurred with higher fre-
quency than in controls without cirrhosis (p=O.O4).
Seventy-nine per cent of peptic ulcer recurrences
were asymptomatic in patients with cirrhosis. There
were no complications during the follow-up period:
this could be due to the regular timing of endoscopy,
which permitted early detection and treatment of the
recurrences, thus preventing further complications.
Key words: Cirrhosis; Peptic ulcer.
0 Journal of Hepatology.
To assess the risk and the clinical characteristics of
peptic ulcer in patients with cirrhosis, we planned the
present survey as part of a large prospective study in
consecutive patients on the prognosis of cirrhosis,
which included serial endoscopic evaluation.
Patients and Methods
Definitions
The diagnosis of active peptic ulcer (PU) was based on
the endoscopic detection of a defect in the duodenal or
gastric wall, with a distinct crater and border. If diag-
nosis of duodenal ulcer was uncertain, histological
examination of biopsies taken from the lesion was used
to rule out erosions (8). The criteria used for the defi-
nition of the benign nature of gastric ulcers are docu-
mented elsewhere (9). The diagnosis of benign gastric
ulcer was always confirmed by histological examin-
ation of two series of at least six biopsies taken from
the border of the ulcer and from the scar after ulcer
healing was achieved, respectively.
633
S. Siring0 et al.
The ulcer was considered to be symptomatic if upper
abdominal pain had been present for at least 7 con-
secutive days at the time of ulcer diagnosis, or if endo-
scopy was required because of upper abdominal pain.
Bleeding was attributed to the peptic ulcer if active
bleeding or a clot on the ulcer was seen at endoscopy, or,
in absence of these signs, if no other lesions (including
varices) were seen in the upper gastrointestinal tract.
The follow-up period was calculated as the interval of
time between the first and the last endoscopy performed
in the study.
All endoscopies were performed by competent endos-
copists, with experience ranging from 5 to 14 years. Al-
though no formal assessment of intra- or inter-observer
variability was made for the diagnosis of peptic ulcer, it
is known that there is good agreement when experienced
endoscopists diagnose peptic ulcer (10).
Survey and treatmentprotocols
From 1 January 1987 to 7 November 1989 all patients
with cirrhosis admitted or seen as out-patients at the 1st
Medical Clinic in Bologna were enrolled in a large on-
going study on the course of cirrhosis. An evaluation of
peptic ulcer was planned as part of this study, as endo-
scopy was scheduled in all patients at entry.
The severity of cirrhosis was assessed using
Campbell’s numerical modification of Child’s classifi-
cation (11). Campbell’s grading system scores each of
the Child criteria from 1 to 3 by increasing severity. Ac-
cording to this scoring system, patients are classified in
class A if the score is up to 8, in class B if the score is 9-
11 and class C if the score is higher than 11.
The planned follow up was to see the patients in the
clinic at 3- or 6-month intervals, unless admission to
hospital was required between visits. Endoscopy was re-
peated yearly in the absence of esophageal varices, and
every 6 months if varices were present or, if a PU was
diagnosed, after ulcer healing, or if clinically indicated.
Only patients who had previous gastric surgery or
no endoscopy during the survey period were excluded
from the study on the course of peptic ulcer.
If an active ulcer was diagnosed, standard thera-
peutic dosage of an anti-H2 receptor drug (ranitidine
300 mg at night) was started and endoscopy repeated
at 4-week intervals in cases of duodenal ulcer (DU)
or pyloric or prepyloric ulcer (P/PPU), and at 8-week
intervals in cases of gastric ulcer (GU), until ulcer heal-
ing was confirmed. After ulcer healing, the patients
were given standard maintenance dosage of the same
H2 blocker (ranitidine 150 mg at night).
Only one patient had P/PPU, and he was included
in the group of patients with DU.
In all patients in whom a diagnosis of PU had been
634
made before entry to the study, the presence of symp-
toms and complications at the time of the first diag-
nosis of the ulcer and subsequent course prior to entry
into the study were retrospectively investigated from
the patient’s history and clinical notes.
During the same evaluation period 167 consecutive
patients without cirrhosis but with DU and 57 con-
secutive with benign GU were diagnosed, and these
formed the control group. The data collection, symp-
toms definition and endoscopic criteria were the same
as in the group with cirrhosis.
Statistical analysis
Results are expressed as proportions for qualitative
data and as means (+-Standard Deviation) for quanti-
tative data. Differences between proportions were
tested by the chi-square test. Differences in mean
values were evaluated by the t-test (2 groups) or one-
way analysis of variance (k groups), respectively The
Duncan’s multiple-range test was used within the one-
way analysis of variance for comparison of mean
values among subgroups. Incidence and prevalence
rates were calculated, in consecutive patients with cir-
rhosis, according to standard methods (12). The an-
nual incidence (number of new ulcers in patients with
cirrhosis at risk) was used to measure the risk of devel-
oping an ulcer over a 1-year period (12). To fully utilize
the period each patient contributed to the study, the
risk was also expressed as person-time incidence (12).
The point prevalence (number of cases diagnosed at
entry) was used to evaluate the immediate probability
of having a peptic ulcer (12), and the period prevalence
(the addition of point prevalence, incidence and recur-
rence rates) to express the burden of peptic ulcer dis-
ease in patients with cirrhosis over the study period
(12). The life-time prevalence is a variant of period
prevalence, being the proportion of subjects who have
the disease at some point during their life (12). In the
present study the life-time prevalence of peptic ulcer,
diagnosed by barium meal or endoscopy, was extended
from the patient’s past history to the end of the study
The relative risk, with a 95% confidence interval (CI)
(13), of having a PU during the study period was
evaluated in relation to the different etiologies of the
cirrhosis and to the severity of liver disease.
Results
Cirrhotic population
Prevalence and incidence of PU. During a 35-month
period, 368 consecutive patients with cirrhosis entered
the study on the course of cirrhosis.
Forty-four patients did not meet the inclusion cri-
teria: 15 patients had previous gastric resection (8 for
 Peptic ulcer in cirrhosis

TABLE 1
entry: 23 (7.1%) DU and 15 (4.6%) benign GU, which
Characteristics of the study population are the relative figures for the point prevalence rates
No. 324 (Table 3).
M/F 219 (67.5%)/105 (32.5%) Thirty-one (9.6%) patients without PU at entry to
Age (years)* 56.1 (SD 13.1)
the study received a previous diagnosis of PU by endo-
Etiology of the cirrhosis
HBV+
scopy - 24 (7.4%) DU and 7 (2.1%) GU - and 6 ( 1.8%)
HBsAg+ 61 (18.8%) showed a duodenal scar in the absence of previous
HBsAg- 85 (26.2%)a demonstration of duodenal ulcer (Table 2).
Alcoholic 86 (26.5%)b
Cryptogenic 79 (24.4%)
The remaining 249 patients without PU, up to the
PBC 9 (2.8%) time of entry into the study, were available for the as-
Others 4 (1.2%) ‘sessment of the incidence rates (Table 2). One hundred
Campbell’s score* 7.5 (SD 2.3) and nine patients who did not receive further endo-
Albumin (g/d])* 3.5 (SD 0.7) scopic examination were excluded: 32 according to the
Bilirubin @mol/l)* 39 (SD 55) schedule planned for the follow up, 39 died, 4 had liver
Prothrombin activity (% reduction)* 32.9% (SD 16.4) transplantation, 28 dropped out and 6 refused any
Ascites 113 (35%) further endoscopic follow up (Table 2). The incidence
Hepatic encephalopathy 35 (11%)
rate was calculated in the remaining 140 patients who
received further endoscopic examination during a
Compromised nutritional status 193 (59.5%)
(good or poor)# mean period of 1.2 (k0.61) years, receiving a mean
Esophageal varices 216 (67%) number of 2.8 endoscopies (total=404). Six (4.3%) de-
veloped PU - 3 (2.1%) DU, 2 (1.4%) GU and 1 (0.7%)
* Mean, in brackets Standard Deviation.
a Patients only with antibodies to HBV b 2 were HBsAg+ and 11 had P/PPU - which corresponds to an incidence of 0.035
antibodies to HBV c 2 had antibodies to HBV. new ulcers per person per year of follow up - 0.025 for
# According to the Child-Campbell classification, nutritional status
DU, 0.01 for GU (Table 3).
was scored as excellent, good and poor. Patients with nutritional sta-
tus good or poor were grouped together. Moreover, 5 of 31 patients with a past diagnosis of
peptic ulcer, and no PU at entry, and all of whom had
endoscopic follow up, had ulcer recurrence during the
study - 3 DU and 2 GU - while none of the 6 patients
with duodenal scar developed PU.
DU, 4 for GU and 3 for gastric carcinoma) and 29 had Therefore, 49 (15.1%) of the 324 patients with cir-
not received endoscopy during the study period, 2 of rhosis who entered the study on the course of peptic
these having previously had GU and DU, respectively. ulcer in cirrhosis had PU: 38 at entry, 6 developed PU
Three hundred and twenty-four patients with cir- and 5 patients, with a previous diagnosis of ulcer, had
rhosis entered the study. Their characteristics are recurrences during the follow-up period. These figures
shown in Table 1. A flow diagram of the patients’ out- correspond to the period prevalence (Table 3).
come is shown in Table 2. As a whole, 89 (24.2%) of the 368 patients with cir-
Thirty-eight (11.7%) of the 324 patients had PU at rhosis who entered the study on the course of cirrhosis

TABLE 2
Flow diagram of the patients’ outcome

No. with DU No. with GU

368 Patients with cirrhosis entered the studv.

t 44 excluded i 15 (gastroresection) - 8t 4t
29 (not endoscoped) 1t 1t
3i4 endoscoped at entry
38 with PU at entry 23*ts 15*tg
31 with past history of PU 24t 7t
- had recurrences during f-u 3* 2*
6 with duodenal scar
I
249 available for the incidence study
109 did not have further endoscopic f-u
I+
140 had regular endosconic f-u 4*t# 2*t#

* Used to calculate period prevalence. t Used to calculate life-time prevalence. * Used to calculate point prevalence. # Used to calculate incidence.

635
S. Siring0 et al.

TABLE 3 TABLE 4
Prevalence and incidence rates of peptic ulcer in patients with cir- Characteristics of the patients with cirrhosis and PU
rhosis
No. 49
Prevalence Incidence M/F 33 (67%)/16 (33%)
Age (years)* 58.4 (SD 11.1)
Point Period Life time 1 year Person/year
(n=324) (n=324) (n=368) (n= 140) (n=l40) Etiology of the cirrhosis
HBV+
DU* 7.1% 9.3% 16.3% 2.8% 0.025% HBsAg+ 14 (28.6%)
GU 4.6% 5.9% 7.9% 1.4% 0.01% HBsAg-” 11 (22.5%)
Total 11.7% 15.1% 24.2% 4.3% 0.035% Alcoholic 15 (30.6%)
Cryptogenic 9 (18.4%)
* Includes one pyloric ulcer.
DU 30 (61%)
GU 19 (39%)
Asymptomatic PU 35 (71%)
had a PU at some point during their life (life-time
First diagnosis of PU made in the study 25 (51%)
prevalence): 14 of 44 patients excluded from the study
because they did not have endoscopy and 75 of 324 Complications from peptic ulcers 10 (20%)
who had endoscopy during the study period (Table 2). First diagnosis of PU with complications 10 (40%)
There were 60 (16.3%) DU and 29 (7.9%) GU over the Operated 1 (10%)
life period of the 368 patients with cirrhosis who were Deceased 1 (10%)
considered for the present study (Table 3). No. of patients taking drugs 16 (32.6%)
Regarding the association between the etiology of Anti-ulcer drugs 12 (24.5%)
NSAID 4 (8.2%)
liver disease and the presence of peptic ulcer among
the 324 patients who had endoscopy, 23% (n= 14; R.R * Mean, in brackets Standard Deviation.
a Patients only with antibodies to HBV
1.7, 95% C.I. 1.0-3.0) of patients with HBsAg+ cir-
rhosis, 13%(n=11;R.R.0.8,95%C.1.0.4-1.5)ofthose
HBsAg-, 17% (n=15; R.R. 1.2, 95% C.I. 0.7-2.1) of
patients with alcoholic cirrhosis and 11% (n=9; R.R. However, patients with cirrhosis and asymptomatic PU
0.7, 95% C.I. 0.4-1.3) of patients with cryptogenic cir- had more advanced liver disease than patients with cir-
rhosis had PU. The frequency of PU among HBsAg+ rhosis without peptic ulcer, although only the ascites
patients was significantly higher (p=O.O5) than in the prevalence reached statistical significance (p = 0.04). Pa-
other groups. No differences were found among the tients with cirrhosis and asymptomatic PU were more
different etiologies if the different types of peptic ulcer decompensated than patients with symptomatic PU
were taken into account. (Campbell score 8.2 vs 6.2; p=O.O07), and no differ-
Table 4 shows the main characteristics of 49 patients ences were found in the complication and mortality
with PU. Thirty-five (71%) patients were asympto- rates.
matic, 25 (51%) had the first diagnosis of PU in the Patients with cirrhosis and DU did not significantly
study. The peptic ulcer complication rate at entry (in differ from those without PU (Table 5). Patients with
all cases a bleeding episode), was 20% in the whole cirrhosis and GU tended to have more advanced liver
group and 40% in those who had not received a pre- disease than patients without PU (Table 5). Patients
vious diagnosis of PU when admitted to the study. with cirrhosis and GU also had a significantly more
Effect ofdrug administration on ulcer-related symp- decompensated liver disease and a higher complication
toms and complications. Sixteen (32.6%) of the 49 pa- rate than those with DU (Table 5).
tients with PU were taking drugs able to alter the clin- Differences were not found between cirrhotic pa-
ical course of the ulcer (Table 4): 12 anti-H2 receptor tients with symptomatic and asymptomatic DU (Table
drugs, 9 of whom (7 of 10 with DU and 2 with GU) 6). Patients with cirrhosis and asymptomatic GU
were asymptomatic, and 4 NSAID 2 (1 of 3 with GU showed more severe liver disease than those who were
and 1 with DU) without symptoms; 4 all taking symptomatic and those without PU (Table 6). No dif-
NSAID, bled from the peptic ulcer. Withdrawing the ferences were found in the complication and mortality
patients taking drugs, 24 (72.7%) of the remaining 33 rates between symptomatic and asymptomatic patients
were asymptomatic and 6 (18.1%) bled from the ulcer. (Table 6).
These figures are not dissimilar to those of the whole To assess whether a more severe liver disease carries
group with PU. an increased risk of peptic ulcer, the 324 patients who
Clinical characteristics. There were no clinical differ- entered the study were stratified according to the
ences between cirrhotic patients with and without PU. Child-Campbell score cut-point of 8 points (Table 7):

636
 Peptic ulcer in cirrhosis

TABLE 5
Severity of liver disease in patients with cirrhosis without peptic ulcer and with different types of ulcers

Without PU With DU With GU P

No. 275 30 19
Campbell’s score* 7.5 (SD 2.3)b 7.0 (SD 2.1) 8.7 (SD 2.6)“,b 0.04
Albumin (g/dl)* 3.5 (SD 0.6)d 3.7 (SD 0.6) 3.1 (SD 0.6pd 0.01
Bilirubin (,umoVl)* 39 (SD 56) 39 (SD 41) 46 (SD 32) 0.8
Prothrombin activity (% reduction)* 32.9 (SD 16.1) 32.1 (SD 18.5) 39.9 (SD 13.9) 0.2
Ascites 94 (34%) 9 (30%) 10 (53%) ns
Hep. encephalopathy 30 (11%) 2 (7%) 3 (16%) ns
Compromised nutritional status (good or poor)1 157 (57%) 18 (60%) 12 (63%) ns
Es. varices 186 (68%) 19 (63%) 14 (74%)
Complications from ulcers 3 (10%) 7 (37%) tfso2
Complications related mortality 0 (0) 1 (5%) ns

* Mean, in brackets Standard Deviation.

a, b, c, d pcO.05 (Duncan test).
t According to the Child-Campbell classification nutritional status was scored as excellent, good and poor. Patients with nutritional status good
or poor were grouped together.

TABLE 6
Severity of liver disease in patients with cirrhosis without peptic ulcer, with different types of ulcer and in relation to the ulcer-related symptoms

Without PU Asympt. DU Sympt. DU Asympt. GU Sympt. GU P

No. 275 21 9 14 5
Campbell’s score* 7.5 (SD 2.3)d 7.3 (SD 2.0) 6.3 (SD 2.3)b 9.6 (SD 2.1yM 6.0 (SD 1.7)” 0.003
Albumin (g/d])* 3.5 (SD 0.6) 3.7 (SD 0.7)’ 3.9 (SD 0.4)x 2.9 (SD 0.5)efs 3.6 (SD 0.4) 0.007
Bilirubin &mol/l)* 39 (SD 56) 38 (SD 43) 39 (SD 41) 51 (SD 26) 31 (SD 7) ns
Prothrombin activity (% reduction)* 32.9 (SD 16.1)h 32.4 (SD 21.6) 31.3 (SD 16.1) 42.4 (SD 9.3)h 33.0 (SD 22.4) ns
Ascites 94 (34%)’ 8 (38%) 1 (11%) 10 (71%)” 0 (0)’
Hep. encephalopathy 30 (11%) 1 (5%) 1 (11%) 3 (21%) 0 (0)
Compromised nutritional status 157 (57%) 14 (67%) 4 (44%) 11 (79%)” 1 (20%)”
(good or poor)?
Es. varices 186 (68%) 12 (57%) 7 (78%) 12 (86%) 2 (40%)
Complications from ulcers 1 (5%) 2 (22%) 5 (36%) 2 (40%)
Complications related mortality 0 (0) 1 (5%) 1 (7%) 0 (0)
* Mean, in brackets Standard Deviation.
a.b*c,d+,f,s,hpcO.05 (Duncan test). i p=O.O06, ’ p=O.O05, m p=O.O2, ” p=O.O4.
t According to the Child-Campbell classification nutritional status was scored as excellent, good and poor. Patients with nutritional status good
or poor were grouped together.

patients with a score value equal to or greater than 8
showed a significantly higher frequency of asympto-
matic ulcers, GU and asymptomatic GU than patients
with a lower score.
Ten (20%) patients had ulcer-related complications:
all had bleeding peptic ulcers, 6 (60%) were asympto-
matic, none underwent surgery because of compli-
cations, and 1 (10%) died. No statistical differences
were found in the severity of liver disease between pa-
tients with and without ulcer complications, although
patients with complicated GU tended to have more de-
compensated cirrhosis than those with uncomplicated
ulcers.
Endoscopic follow up. Thirty-eight of the 49 patients
with cirrhosis and PU had endoscopic confirmation of
ulcer healing. Four of the remaining 11 patients refused
further endoscopic follow up, 6 died before having
endoscopic confirmation of ulcer healing - 5 of hepatic
causes and 1 of bleeding GU - and 1 patient had gas-
tric surgery because of a suspicion of gastric
lymphoma.
Twenty-three of these 38 patients had DU (Table 8);
all received full dosage H2-receptor antagonist treat-
ment. The 4-week healing rate was of 90%, while those
with a non-healed ulcer had endoscopic confirmation
of ulcer healing 4 weeks later.
All 15 patients with cirrhosis and GU received full
dosage anti-H2 therapy (Table 8). In all, endoscopy
was repeated after 8 weeks. The healing rate was 67%.
In all patients with a non-healed ulcer a repeat endo-
scopy confirmed ulcer healing within 31 weeks.
After the endoscopic confirmation of ulcer healing,
31 patients with cirrhosis, 19 with DU and 12 with
GU had regular endoscopic follow-up: there were 14

637
S. Siring0 et al.

TABLE I
Risk of having a peptic ulcer in relation to the severity of cirrhosis as expressed by a Child-Campbell score ~8 (n= 135) and <8 (n= 189)

0 5% 10% 15% 20% P Relative risk 95% confidence intervals

Peptic ulcer ns 1.29 0.77-2.14

Sympt. ulcer ns 0.37 0.11-1.22

Asympt. ulcer 0.04 2.02 1.09-3.74

DU ns 0.78 0.39-1.58

Sympt. DU ns 0.39 0.09-l .72

Asympt. DU ns 1.04 0.45-2.40

GU 0.01 3.21 1.32-7.79

Sympt. GU ns 0.92 0.165.44

Asympt. GU 0.005 5.43 1.78-16.50

II I
n score X3 0 score ~8.

recurrences, 11 (79%) asymptomatic, none with com- GU had endoscopy after 8 weeks of anti-H2-receptor
plications. Five of the remaining 7 patients died of hep- antagonist full-dosage therapy with a healing rate of
atic causes before having further endoscopy and two, 84% (Table 8). There were no statistical differences
according to the schedule’s follow up, still have to have with respect to the DU and GU healing rates observed
the first endoscopy after the ulcer healing. Table 9 in patients with and without cirrhosis (Table 8).
shows the recurrence rate observed during the follow- Seventy-six of 120 patients without cirrhosis with
up period. Since the anti-ulcer therapy was discon- DU and 20 of the 57 patients without cirrhosis with
tinued by some patients, the results were analyzed ac- benign GU, according to the schedule planned for the
cording to the period of time spent in treatment. follow up, had further endoscopic examination after
ulcer healing. Table 9 shows the recurrence rates.
Population without cirrhosis Although patients with cirrhosis and GU had a
One-hundred and twenty-four of the 167 patients with- higher recurrence rate than patients without cirrhosis,
out cirrhosis and with DU, all treated with H2-receptor the difference was not significant. However, taking into
antagonist full dosage therapy, had endoscopy to con- account the recurrences during the follow-up period
firm ulcer healing (Table 8). Eighty-eight had endo- in which both groups were kept on anti-H2-receptor
scopy after 4 weeks, with a healing rate of 82%. In the antagonist therapy, patients with cirrhosis with GU
remaining 36 patients ulcer healing was confirmed by had significantly more recurrences than patients with-
endoscopy within 8 weeks. out cirrhosis (Table 9).
All of the 57 patients without cirrhosis with benign
Discussion
Peptic ulcer prevalence
TABLE 8 Only a few endoscopic studies have been done to assess
Peptic ulcer healing rates in patients with cirrhosis and controls
the prevalence rate of gastro-duodenal lesions in
asymptomatic normal subjects. Two of these studies
Healing rates
dealt with over 300 young, healthy asymptomatic vol-
No. 4- or 8-week Overall
unteers (14,15) and one with 659 relatives of gastric
healine rates healine
cancer patients and controls with no reference to the
DU (patients with cirrhosis) 23 90%* 100%
DU (patients without cirrhosis) 124 82%* 100%
ulcer-related symptoms (16). In these series the point
GU (patients with cirrhosis) 15 67%’ 100% prevalence of PU ranged from 1.12% to 1.97%. The
GU (patients without cirrhosis) 57 84%’ 98% point prevalence of PU in patients with cirrhosis has
* 4-week healing rates. # I-week healing rates. been reported to be increased with respect to the nor-

638
 Peptic ulcer in cirrhosis

TABLE 9
Peptic ulcer recurrence rates in patients with cirrhosis and controls

Recurrence rates

Overall While undergoing treatment

No. No with No of F-U (weeks)* No. No with No of F-U (weeks)*

recurrences (%) recurrences recurrences (“IO) recurrences

DU (patients with cirrhosis) 19 6 (31.5%) 8 62.1 (SD 40.0) 19 4 (21%) 6 50.5 (SD 35.8)
DU (patients without 16 21 (28%) 21 62.9 (SD 14.4) 16 13 (17%) 13 51.3 (SD 20.0)
cirrhosis)
GU (patients with cirrhosis) 12 6 (50%) 6 39.1 (SD 15.6) 11 6 (54.5%) 6 39.9 (SD 16.1)
GU (patients without 20 6 (30%) 6 42.4 (SD 21.2) 20 4 (20%) 4 36.5 (SD 21.3)
cirrhosis)

* Mean, in brackets Standard Deviation.

a p=o.o4.

ma1 population, ranging from 6.3% to 15% (l-7), simi-
lar to our findings of 11.7%. Our endoscopic survey
was based on consecutive patients, so that both symp-
tomatic and asymptomatic ulcers were discovered.
Phillips et al. (2) assessed the effect of porta-caval
shunt on the risk of developing peptic ulcer by review-
ing five studies involving 511 patients with cirrhosis.
They found an overall 20% life-time prevalence of PI-J,
which is similar to the 24.2% life-time prevalence found
in our study, and much higher than the 3.5% life-time
prevalence of PU found in patients without cirrhosis
(16).
Thus, many studies show that peptic ulcer preva-
lence is increased in patients with cirrhosis. Prevalence,
however, merely reflects the number of cases, while the
risk of developing PU is better estimated by the inci-
dence rate.
Peptic ulcer incidence
In our study, the incidence rate of PI-I, during a mean
period of 1.2 (20.61) years, was 4.3% - 2.8% for both
DU and P/PPU, and 1.4% for GU - which accounts
for an incidence of new ulcers of 0.035 per person-year,
similar to that calculated retrospectively by Phillips in
patients with cirrhosis (2).
Unfortunately, no prospective endoscopic studies on
the incidence of PU are available in normal subjects.
The best studies in this field come from Denmark,
where new cases of PU, diagnosed by barium meal or
surgery in people older than 15 years, were collected
retrospectively (17,18). The annual incidence rate of
PU in this population was 0.17% - 0.13% for both DU
and P/PPU and 0.03% for GU. There seems to be a
25-fold increase in the annual incidence of PU in our
patients with cirrhosis - a 20-fold increase in DU and
a 47-fold increase in GU incidence - although the re-
ported incidence rates in the Danish studies are prob-
ably an underestimate. In fact, only symptomatic pa-
tients presumably underwent radiological examination,
which is less accurate than endoscopy in diagnosing
peptic ulcer. Moreover, retrospective surveys usually
give lower values of incidence rates than prospective
surveys, where well-defined follow-up schedules are ap-
plied and ulcers are carefully sought (19). However, the
differences in the observed incidence rates of PU in
patients with cirrhosis and those reported in the
Danish study are too large to be explained by the
above-mentioned biases. Thus, it can be concluded that
cirrhosis gives an increased risk of developing peptic
ulcer. Moreover, we found an increased frequency of
PU among patients with HBsAg+ cirrhosis, contrary
to what has been reported by some studies (1,3-6), but
not by others (7). Unfortunately, at the time when the
present study was done the test to detect antibodies to
HCV in serum was still not available, so that we were
not able to evaluate the potential role of HCV infec-
tion as a risk factor for PU in patients with cirrhosis.
However, 70%80% of patients without any known
etiological factor for chronic liver disease (cryptogenic
cirrhosis) have antibodies to HCV (20,21). In our own
experience, antibodies to HCV were detected in 80% of
the patients with cryptogenic cirrhosis and in 76% of
those who had antibodies only to HBV (22). In the
present study neither patients with cryptogenic cir-
rhosis nor those with antibodies only to HBV had a
significantly high frequency of PU. Thus, it may be
possible that the HCV infection in patients with cir-
rhosis does not carry an increased risk of peptic ulcer.
It has already been shown that Helicobacter pylori
is strongly associated with duodenal or gastric ulcer
(23). Little is known at the present time about the poss-
ible relationship of Helicobacter pylori with chronic
liver disease and endoscopic findings in patients with
cirrhosis. To our knowledge only two studies have as-
sessed these relations, with conflicting conclusions. The
first one included 44 consecutive patients with cir-

639
S. Siring0 et al.
rhosis, and 43% had gastric erosions and/or peptic ul-
cer at endoscopy (24). Helicobacter pylori was iden-
tified in the gastric biopsies of 77.3% of the patients:
in 89% of those with gastric erosions and/or peptic ul-
cer, and in 68% of patients with cirrhosis without
endoscopic lesions (24). In the second study Helico-
batter pylori was found in the antral biopsies of 26%
of 74 patients with cirrhosis and without peptic ulcer,
and only 19% of whom had, if any, gastric mucosal
erosions (25). In this study Helicobacter pylori was as-
sociated with histological gastritis but not with endo-
scopic hypertensive gastropathy (25).
Further surveys are needed to assess the possible re-
lationship between Helicobacter pylori infection and
chronic liver disease and the associated endoscopic
findings.
Peptic-ulcer-related symptoms and complications
There are some surprising findings in our study with
regard to the frequency of asymptomatic ulcers and the
high complication rate from ulcer among patients with
cirrhosis. Seventy-one percent of patients with cirrhosis
and PU were asymptomatic and 20% had ulcer-related
complications. Complications occurred in 60% without
symptoms and in 40% of those in whom the diagnosis
of PU was made for the first time. One can wonder
whether such a high proportion of asymptomatic ul-
cers and complications might depend on the drugs
(H2-antagonist, NSAID) that 32.6% of patients with
cirrhosis and ulcer were taking when the ulcer was di-
agnosed. However, even excluding the patients taking
these drugs, the proportion of those with asympto-
matic ulcers and with complications did not change.
The presence of ulcer-related symptoms and the oc-
currence of complications seemed to be related to the
degree of liver function impairment. In fact, patients
with asymptomatic ulcers had a more decompensated
liver disease than patients with cirrhosis without ul-
cers or those with symptomatic ulcers. The same ten-
dency was observed regarding the occurrence of com-
plications, although it did not reach statistical sig-
nificance, probably because of the smaller number of
patients. On the other hand, patients with more de-
compensated cirrhosis (Child-Campbell’s score =8)
had a higher frequency of asymptomatic ulcers and
GU.
The clinical implication of these findings is that pa-
tients with more decompensated cirrhosis have a
higher frequency of silent ulcers and complications.
Peptic ulcer healing and recurrence rates
During a l-year period after ulcer healing, almost 50%
of the patients had ulcer recurrences, 79% of these were
640
asymptomatic and none had complications despite the
fact that at entry the complication rate was 20%. This
may be explained by the regular endoscopic follow up,
since endoscopy was done at regular intervals so that
recurrent ulcers, which were initially asymptomatic in
79% of cases, were diagnosed and treated before they
could give rise to complications.
In relation to the types of ulcer, patients with GU
had more severe liver disease, higher complication
rates, slower healing and higher recurrence rates than
patients with DU. We do not have any explanation for
this behavior.
In conclusion, endoscopic follow up in patients with
cirrhosis should be planned, bearing in mind that cir-
rhosis carries an increased risk of peptic ulcer, which is
asymptomatic in most cases and often has intercurrent
complications. To date, there is evidence that a regular
endoscopic follow up in patients with cirrhosis is useful
for monitoring the progression of the risk of bleeding
from esophageal varices (26-28). The present work
shows that regular endoscopic surveillance is also
needed to diagnose new ulcers and recurrences, in or-
der to prevent complications. However, whether this
strict surveillance policy is cost effective, in terms of
reducing hospitalization and improving survival of pa-
tients with cirrhosis, remains to be established.
Acknowledgement
Part of this work was presented at the “Spring Meet-
ing” of the British Society of Gastroenterology held in
Warwick (Coventry, U.K.) 28-30 March 1990.
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