Natural history of major complications in hepatitis C virus-related cirrhosis evaluated by per-rectal portal scintigraphy.

Abstract

To examine the correlation between the porto-systemic hypertension evaluated by portal shunt index (PSI) and life-threatening complications, including hepatocellular carcinoma (HCC), liver failure (Child-Pugh stage progression), and esophagogastric varices.
Two hundred and twelve consecutive subjects with HCV-related cirrhosis (LC-C) underwent per-rectal portal scintigraphy. They were allocated into three groups according to their PSI: group I, PSI< or =10%; group II, 10%<PSI<30%; and group III, 30%< or =PSI. Of these, selected 122 Child-Pugh stage A (Child A) subjects were included in analysis (a mean follow-up period of 5.9+/-5.4 years, range 6 mo-21 years).
No significant correlation between PSI and cumulative probability of HCC incidence was observed. Cumulative probability of Child A to B progression was tended to be higher in group III than in group I, and significantly higher in group III than in group II (62% vs 34%, 62% vs 37%; P = 0.060, <0.01; respectively). Cumulative probability of varices tended to be higher in group III than in group I (31% vs 12%, P = 0.090). On multivariate analyses, significant correlation between PSI and Child A to B progression was observed, and no significant correlation between PSI and HCC incidence or varices progression was observed.
Patients with LC-C of Child A will progress to Child B rapidly after their PSI reaches 30% or higher. PSI can be used to predict occult progressive porto-systemic shunting and liver failure non-invasively. It indicates that PSI may play an important role in follow-up of the porto-systemic hypertension gradient for outpatients with LC unlike hepatic venous catheterization.

Full text

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• VIRAL HEPATITIS •
Natural history of major complications in hepatitis C virus-related
cirrhosis evaluated by per-rectal portal scintigraphy
Etsushi Kawamura, Daiki Habu, Takehiro Hayashi, Ai Oe, Jin Kotani, Hirotaka Ishizu, Kenji Torii, Joji Kawabe, Wakaba
Fukushima, Takashi Tanaka, Shuhei Nishiguchi, Susumu Shiomi
ELSEVIER
PO Box 2345, Beijing 100023, China World J Gastroenterol 2005;11(25):3882-3886
www.wjgnet.com
wjg@wjgnet.com © 2005 The WJG Press and Elsevier Inc. All rights reserved.
World Journal of Gastroenterology ISSN 1007-9327
Etsushi Kawamura, Takehiro Hayashi, Ai Oe, Jin Kotani,
Hirotaka Ishizu, Kenji Torii, Joji Kawabe, Susumu Shiomi,
Department of Nuclear Medicine, Graduate School of Medicine, Osaka
City University, 1-4-3, Asahimachi, Abenoku, Osaka 545-8585, Japan
Daiki Habu, Shuhei Nishiguchi, Department of Hepatology,
Graduate School of Medicine, Osaka City University, 1-4-3, Asahimachi,
Abenoku, Osaka 545-8585, Japan
Wakaba Fukushima, Takashi Tanaka, Department of Public
Health, Graduate School of Medicine, Osaka City University, 1-4-
3, Asahimachi, Abenoku, Osaka 545-8585, Japan
Supported by the Study Group of Portal Malcirculation supported
by Ministry of Health, Labour and Welfare
Correspondence to: Dr. Etsushi Kawamura, Department of Nuclear
Medicine, Graduate School of Medicine, Osaka City University, 1-
4-3, Asahimachi, Abenoku, Osaka 545-8585,
Japan. etsushi-k@med.osaka-cu.ac.jp
Telephone: +81-6-66453885 Fax: +81-6-66460686
Received: 2004-12-07 Accepted: 2004-12-20
AbstractAbstract
AbstractAbstract
Abstract
AIM: To examine the correlation between the porto-systemic
hypertension evaluated by portal shunt index (PSI) and
life-threatening complications, including hepatocellular
carcinoma (HCC), liver failure (Child-Pugh stage progression),
and esophagogastric varices.
METHODS: Two hundred and twelve consecutive subjects
with HCV-related cirrhosis (LC-C) underwent per-rectal portal
scintigraphy. They were allocated into three groups according
to their PSI: group I, PSI
10%; group II, 10%<PSI<30%;
and group III, 30% PSI. Of these, selected 122 Child-Pugh
stage A (Child A) subjects were included in analysis (a mean
follow-up period of 5.9±5.4 years, range 6 mo-21 years).
RESULTS: No significant correlation between PSI and
cumulative probability of HCC incidence was observed.
Cumulative probability of Child A to B progression was
tended to be higher in group III than in group I, and
significantly higher in group III than in group II (62% vs
34%, 62% vs 37%; P = 0.060, <0.01; respectively).
Cumulative probability of varices tended to be higher in
group III than in group I (31% vs 12%, P = 0.090). On
multivariate analyses, significant correlation between PSI
and Child A to B progression was observed, and no significant
correlation between PSI and HCC incidence or varices
progression was observed.
CONCLUSION: Patients with LC-C of Child A will progress
to Child B rapidly after their PSI reaches 30% or higher.
PSI can be used to predict occult progressive porto-systemic
shunting and liver failure non-invasively. It indicates that
PSI may play an important role in follow-up of the porto-
systemic hypertension gradient for outpatients with LC
unlike hepatic venous catheterization.
© 2005 The WJG Press and Elsevier Inc. All rights reserved.
Key words: Portal shunt index; Porto-systemic shunting;
Per-rectal portal scintigraphy; Natural history; Liver cirrhosis;
HCV; Hepatocellular carcinoma; Liver failure; Varix
Kawamura E, Habu D, Hayashi T, Oe A, Kotani J, Ishizu H, Torii
K, Kawabe J, Fukushima W, Tanaka T, Nishiguchi S, Shiomi S.
Natural history of major complications in hepatitis C virus-related
cirrhosis evaluated by per-rectal portal scintigraphy. World J
Gastroenterol 2005; 11(25): 3882-3886
http://www.wjgnet.com/1007-9327/11/3882.asp
INTRODUCTIONINTRODUCTION
INTRODUCTIONINTRODUCTION
INTRODUCTION
Hepatitis C virus (HCV) is the most common cause of chronic
liver disease in several countries, including Japan, and chronic
hepatitis due to HCV (CH-C), which exhibits a variable
natural course, is becoming a subject of worldwide interest.
CH-C progresses to cirrhosis of the liver (LC), and may be
complicated by hepatocellular carcinoma (HCC), hepatic
decompensation, and esophagogastric varices[1,2], although
its clinical course has not been fully defined. Despite treatment
such as injection of interferon plus oral ribavirin[3], many
patients with CH-C progress to cirrhosis[4], and develop portal
hypertension as CH-C advances to the early phase of LC[5].
Portal hypertension evaluated by “invasive” hepatic
venous pressure gradient (HVPG) is associated with
progression of liver failure and death[6-8]. Using the method
described in this study, the extent of porto-systemic shunting
(PSS) can be evaluated with the portal shunt index (PSI)
using relatively “non-invasive” per-rectal portal scintigraphy
with 99mTc pertechnetate, because PSI correlates strongly
with portal pressure[9,10]. This study monitored three life-
threatening complications of LC, including the incidence
of HCC, Child-Pugh stage progression, and progression of
esophagogastric varices, and examined the correlation
between PSI and these three complications.
MAMA
MAMA
MATERIALS AND METHODS
TERIALS AND METHODS
TERIALS AND METHODSTERIALS AND METHODS
TERIALS AND METHODS
Patients
A retrospective cohort study was performed on 212 subjects
with HCV-related cirrhosis (LC-C), who were admitted to

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our hospital during the 24 years between March 1979 and
June 2002, and who were evaluated with PSI obtained by
per-rectal portal scintigraphy with 99mTc pertechnetate. These
subjects were diagnosed by examination of liver specimens
obtained by laparoscopy, or needle biopsy performed under
ultrasonic guidance. Exclusion criteria for this study were
as follows: other causes of cirrhosis such as HBV, autoimmune
disease, any alcohol consumption; past treatment with
interferon, endoscopic sclerotherapy or open surgery for
varices; and trans-arterial embolization or open surgery for
HCC. Within a week of hospitalization, all subjects underwent
abdominal ultrasonography for detection of ascites, Child-
Pugh staging as an index of liver failure and endoscopy for
detection of esophagogastric varices[11]. Three Child-Pugh
stages were considered: stage A (score 5-6), stage B (7-9),
and stage C (10-15). The 212 subjects with cirrhosis were
distributed as follows: Child-Pugh stage A (Child A), 122;
Child B, 73; and Child C, 17. At entry, we used other possible
predictors of LC prognosis, including sex, age, serum albumin,
total bilirubin (T-bil), prothrombin time (PT), and platelets[12].
Longitudinal study
We selected 122 Child A subjects for a longitudinal study;
these subjects gave their informed consent to participate,
and agreed to return after discharge to our outpatient clinic
for monitoring. The procedures were approved by the Ethics
Committee of Graduate School of Medicine, Osaka City
University. A total of 122 subjects were monitored for a
mean period of 5.9±5.4 years (range 6 mo to 21 years).
Monitoring was maintained for each evaluation until
confirmation of HCC, or Child A to B progression, or
varices progression, or the end of the outcome observation
period (June 2002). Subjects were excluded from the study
if they were followed by another hospital, or their monitoring
periods were less than 6 mo.
After excluding dropouts, we were able to monitor the
following subjects for at least 6 mo: for HCC incidence,
108 subjects; for Child A to B progression, 107; and for
varices progression, 109. A PSI value of 10% or higher is
considered to be abnormal[9], and a PSI of 30% or higher
has an especially poor prognosis for chronic liver diseases[5].
We defined three groups according to their PSI: group I,
PSI
10%; group II, 10%<PSI<30%; and group III, 30%
PSI. The subjects were further divided as follows: for
HCC incidence, 108 subjects-group I, 33; group II, 41; and
group III, 34; for Child A to B progression, 107 subjects-
group I, 32; group II, 41; and group III, 34; for varices
progression, 109 subjects-group I, 33; group II, 41; and
group III, 35. These subjects underwent the following
examinations: laboratory studies and physical assessment
of the extent of hepatic encephalopathy for Child’s staging,
with a mean interval of 4.1±0.8 mo; abdominal ultrason-
ography or dynamic CT for assessment of the extent of
ascites or the existence of HCC, with a mean interval of
2.1±0.6 mo; and endoscopy for varices, with a mean interval
of 8.1±2.1 mo. HCC was confirmed by histology obtained
by needle biopsy performed under ultrasonic guidance, or
confirmed by selective angiography. The extent of hepatic
encephalopathy was defined from detection of tremor
and/or disorientation by physicians. The extent of ascites
was confirmed by abdominal ultrasonography and/or
physical assessment. We defined progression (or incidence)
of each complication as the first confirmation of HCC, or
Child B or a new variceal factor[13]. Figure 1 shows flow of
participants through monitoring.
Measurement of the portal shunt index
The subjects fasted after the evening meal on the day before
examination. In the morning, the rectum was emptied by
administration of a laxative. First, 370 MBq of 99mTc
pertechnetate (2 mL solution) was given per rectum through
a polyethylene tube (Nélaton’s catheter, French 16) into
the upper rectum, followed by 15 mL of air. Time–activity
curves for the heart and liver areas were obtained every 4 s
using a large-field scintillation camera (Vertex-Plus, ADAC
Laboratories, Silicon Valley, USA). It was equipped with a
low-energy, multipurpose, parallel-hole collimator and was
interfaced with a digital computer. The camera was positioned
over the patient’s abdomen so that the field of view included
the heart, liver, and spleen. At the end of the 5-min examination,
a 5-min summed color image was recorded. To measure
the extent of PSS by PSI, we calculated the number of
counts for the heart as a percentage of the counts for the
heart and liver integrated for 24 s immediately after the
appearance of the liver time-activity curve[9].
Statistical analysis
Results were analyzed by SAS 8.12 statistical software (SAS
Figure 1 Flow of monitoring, group I, PSI
group III, 30% PSI. LC-C, HCV-related cirrhosis; Child A, Child-Pugh stage
10%; group II, 10%<PSI<30%;
A; PSI, portal shunt index.
212 LC-C subjects screened
122 Child A
73 Child B
17 Child C
For a longitudinal study
122 Child A selected.
Follow period: 5.9±5.4 yr
For HCC incidence
14 excluded
For Child A to B progression
15 excluded
13 excluded
For varices progression
108 included in analysis.
33 group I
41 group II
34 group III
Intervals: 4.1±0.8 mo
107 included in analysis.
32 group I
41 group II
34 group III
Intervals: 2.1±0.6 mo
109 included in analysis.
33 group I
41 group II
35 group III
Intervals: 8.1±2.1 mo
Kawamura E et al. Major complications in HCV-related cirrhosis 3883

Page 3

Institute Inc., Cary, NC)[14,15]. Data were expressed as
mean±SD. Comparisons between PSI groups were made
by the Kruskal-Wallis test, the Mantel-Haenszel test, or
ANOVA. The cumulative progression rates were calculated
and plotted by the Kaplan-Meier method, and were compared
by the log-rank test. Any significant variable was considered
suitable for the multivariate analysis using Cox’s regression
model. P<0.05 was taken as statistically significant.
RESULRESUL
RESULRESUL
RESULTS
Patient characteristics at entry
TS
TSTS
TS
Table 1 presents patient data at entry classified by PSI. The
differences between the PSI groups were significant for the
following parameters: age, albumin, T-bil, platelets (P<0.01,
<0.01, <0.05, and <0.01, respectively).
Cumulative progression
No significant correlation between PSI and cumulative
probability of HCC incidence was observed (Figure 2A).
Cumulative probability of Child A to B progression was
tended to be higher in group III than in group I, and
significantly higher in group III than in group II (62% vs 34%,
62% vs 37%; P = 0.060, <0.01; respectively) (Figure 2B).
Cumulative probability of esophagogastric varices tended
to be higher in group III than in group I (31% vs 12%,
P = 0.090) (Figure 2C).
Morbidity
Table 2 presents the proportions of Child A to B progression
and relative risks as uni- and multivariates of possible
predictors, which were classified at the entry of the study.
The total proportion of each predictor, except PSI, was divided
into two between better (upper line) and worse (lower line)
at a cut-off value according to Child staging, or reports by
other authors: for instance, albumin, at 3.5 g/dL[11,12,16].
Group III had the highest rate of Child A to B progression
(21 of 34, 61.8%), followed by <3.5 albumin (50.0%), and
<100 PT (48.8%) (Table 2). A significant relationship was
found between group (I+II) and group III (crude RR = 2.44,
95%CI = 1.33-4.48, P<0.01), and between group II and group
III (2.95, 1.40-6.24, P<0.01), with a trend of significance
(P<0.05). No significant increase of other predictors was
revealed. PSI and the common useful predictors such as
albumin and platelets were included in multivariate analysis;
only group III remained significant (adjusted RR = 2.98,
95%CI = 1.29-6.87, P<0.05).
The group with <10 platelets had the highest incidence
of HCC and the highest progression of varices (30.3%,
47.1%, respectively). On multivariate analyses, no significant
associations were found between PSI and incidence of HCC
or progression of esophagogastric varices.
DISCUSSION DISCUSSION
DISCUSSIONDISCUSSION
DISCUSSION
Even if physical symptoms and serum biochemical tests
indicate the early phase of LC-C, the patient may already have
occult advanced hepatic damage. PSI is a possible predictor
of occult progressive stages of LC-C for outcome patients.
While PSI obtained by per-rectal portal scintigraphy has its
own weaknesses (it emphasizes PSS via the inferior mesenteric
vein, rather than via the superior mesenteric vein, and
Table 1 Characteristics by portal shunt index at entry
Group I
PSI
Group IIGroup III
10% 10%<PSI<30% 30%PSI P
Sex (Male/ Female), n
Age, yr
Albumin, g/ dL
Total bilirubin, mg/ dL
Prothrombin time, %
Platelets, / mm3
25/ 13
48.4±11.7
4.0±0.5
0.8±0.3
95.4±17.2
16.4±5.7
31/ 15 30/ 8
54.9±9.9
3.6±0.4
1.1±0.4
92.5±20.2
10.6±5.0
NS
<0.01
<0.01
<0.05
NS
<0.01
2
1
3
1
1
1
54.3±13.0
4.0±0.3
0.9±0.4
94.5±15.5
14.7±6.9
ANOVA: analysis of variance, PSI: portal shunt index, NS: not significant. Data are expressed as mean±SD. 1Kruskal-Wallis test, 2Mantel-Haenszel test, 3ANOVA.
Figure 2 The probability of each life-threatening com plication. A: The cum ulative
incidence rate of HCC (n = 108). B: The cumulative progression rate of Child A
to B (n = 107). C: The cumulative progression rate of esophagogastric varices
(n = 109). The continuous line shows group I (PSI 10%); the large dotted line
shows group II (10%<PSI<30%); and the sm all dotted line shows group III (30%
PSI). Child A, Child-Pugh stage A; PSI, portal shunt index; pts, patients; GI,
group I; GII, group II; GIII, group III; NS, not significant.
100
80
60
40
20
0
Probability of HCC incidence (%)
G I vs
G II
G I vs
G III
G II vs
G III
all P : NS
Group III
8/34 pts (24%)
6/33 pts (18%)
Group II
6/41 pts (15%)
0 5 10 15 20 25
Time (yr)
Group I
100
80
60
40
20
0
Probability of Child A to
B progression (%)
15/41 pts (37%)
Group III
21/34 pts (62%)
Group II
11/32 pts (34%)
Group I
G I vs
G II
G I vs
G III
G II vs
G III
NS
P = 0.060
P <0.01
0 5 10 15 20 25
Time (yr)
60
50
40
30
20
10
0
Probability of varices progression (%)
0 5 10 15 20 25
Time (yr)
G I vs
G II
G I vs
G III
G II vs
G III
NS
P = 0.090
NS
11/35 pts (31%)
Group III
Group II
Group I
4/33 pts (12%)
9/41 pts (22%)
ACB
3884 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol July 7, 2005 Volume 11 Number 25

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expresses the extent of PSS indirectly), it should be useful
for the observation of LC-C because it is a simple and non-
invasive technique unlike hepatic venous catheterization[9].
In this study, we used 99mTc pertechnetate for per-rectal
portal scintigraphy because of its short half-life and low
cost[17]. Our study had three major findings.
First, there was no correlation between the porto-systemic
hypertension and HCC incidence. This finding suggests that
HCC occurs independently of the decrease in hepatic blood
flow due to the development of PSS.
Second, patients with LC-C of Child A will progress to
Child B rapidly after their PSI reaches 30% or higher. Shiomi
et al.[5], have reported that changes in the portal hemodynamics
of chronic liver disease subjects were not gradual. The
development of PSS causes hepatic functional reserve to
deteriorate rapidly. We propose that per-rectal portal
scintigraphy is useful to predict occult progressive portal
hypertension and liver failure in the early phase of LC-C,
on the basis of the strong relationship between PSI and the
Child-Pugh staging.
Third, the natural advance of PSS has relevance to
esophagogastric varices progression in patients with the early
phase of LC-C. Other authors have reported that the porto-
systemic pressure gradient is a strong predictor for varices
progression[18,19]. But in this study, PSI showed no statistical
advantage over platelets, albumin, or T-bil for detecting the
progression of varices. The reason why PSI was worse than
these laboratory data is because esophagogastric varices
mainly reflect the flow of superior mesenteric vein.
Progressive viral hepatitis has been acknowledged as a
major indication for liver transplantation[20,21]. Kiuchi et al.[22],
have emphasized the need to evaluate the recipients
preoperatively. One of the important recipient factors is
the presence of collateral circulation[23]. Bruix et al.[24], have
reported that LC patients with increased portal pressure
are at high risk of hepatic decompensation after resection
of HCC. We propose that preoperative per-rectal portal
scintigraphy would be useful for early detection of occult
portal hypertension, to assess graft size requirement to
prevent graft failure after liver transplantation, or to avoid
liver failure after hepatectomy.
In summary, physicians can monitor the porto-systemic
hypertension gradient in LC patient during the outcome
observation period by using “non-invasive” per-rectal portal
scintigraphy; on the other hand, measurement of HVPG
needs hospitalization. In the early phase of LC-C, PSI can
be used to predict occult progressive PSS and liver failure.
Therefore, even for patients diagnosed as being in the early
phase of LC-C on the basis of other indicators, those with
an initial PSI
30% should be observed by keeping early
liver transplantation, or liver failure after hepatectomy in
mind; HCC should be watched for, regardless of PSI.
REFERENCESREFERENCES
REFERENCESREFERENCES
REFERENCES
1Sorbi D, Gostout CJ, Peura D, Johnson D, Lanza F, Foutch
PG, Schleck CD, Zinsmeister A R. A n assessment of the
management of acute bleeding varices: a multicenter pro-
spective member-based study. Am J Gastroenterol 2003; 98:
2424-2434
Davis GL, Albright JE, Cook SF, Rosenberg DM. Projecting
future complications of chronic hepatitis C in the United States.
Liver Transpl 2003; 9: 331-338
Fattovich G, Zagni I, Minola E, Felder M, Rovere P, Carlotto
A, Suppressa S, Miracolo A, Paternoster C, Rizzo C, Rossini
A , Benedetti P, Capanni M, Ferrara C, Costa P, Bertin T,
Pantalena M, Lomonaco L, Scattolini C, Mazzella G, Giusti
M, Boccia S, Milani S, Marin R, Lisa Ribero M, Tagger A. A
randomized trial of consensus interferon in combination with
ribavirin as initial treatment for chronic hepatitis C. J Hepatol
2003; 39: 843-849
Iino S. Natural history of hepatitis B and C virus infections.
Oncology 2002; 62: 18-23
Shiomi S, Sasaki N, Habu D, Takeda T, Nishiguchi S, Kuroki
T, Tanaka T, Ochi H. Natural course of portal hemodynam-
ics in patients with chronic liver diseases, evaluated by per-
rectal portal scintigraphy with Tc-99m pertechnetate. J
Gastroenterol 1998; 33: 517-522
Debernardi-V enon W, Bandi JC, Garcia-Pagan JC, Moitinho
2
3
4
5
6
Table 2 Relative risks of possible predictors for Child-Pugh stage A to B progression
Classification ofProportion of Child-Pugh
1Relative risks
predictor at entry stage A to B progression, n/ N (%) Crude RR (95%CI)
2Adjusted RR (95%CI)
Sex Female
Male
16/ 34 (47.1)
31/ 73 (42.5)
1.00
1.47 (0.76-2.84)
0.99 (0.96-1.01)
1.00
1.49 (0.83-2.67)
1.00
1.27 (0.68-2.39)
1.00
1.06 (0.59-1.91)
1.00
1.60 (0.81-3.16)
1.51 (0.65-3.51)
1.00
2.95 (1.40-6.24)b
(P trend <0.05)
1.00
2.44 (1.33-4.48)d
Age (per 1 yr)
Albumin, g/ dL 3.5+
<3.5
<1.0
1.0+
100+
<100
10+
<10
Group I
Group II
Group III
25/ 63 (39.7)
22/ 44 (50.0)
32/ 69 (46.4)
15/ 38 (39.5)
27/ 66 (40.9)
20/ 41 (48.8)
32/ 73 (43.8)
13/ 32 (40.6)
11/ 32 (34.4)
15/ 41 (36.6)
21/ 34 (61.8)
1.00
0.98 (0.49-1.95)
Total bilirubin, mg/ dL
Prothrombin time, %
Platelets, / mm3
1.00
1.40 (0.68-2.86)
1.67 (0.70-3.99)
1.00
2.98 (1.29-6.87)a
(P trend: NS)
1.00
2.36 (1.17-4.78)c
Portal shunt index
Group (I+II)
Group III
26/ 73 (35.6)
21/ 34 (61.8)
aP<0.05 vs Group II PSI, bP<0.01 vs Group II PSI, cP<0.05 vs Group (I+II) PSI, dP<0.01 vs Group (I+II) PSI, NS: not significant. 1RR and their 95% CI were determined by a
Cox’s regression model. 2This model includes albumin, platelets, PSI. Group I, PSI
Confidence interval, RR: Relative risk, PSI: Portal shunt index, n; progression proportion, N; total proportion.
10%; Group II, 10%<PSI<30%; Group III, 30%PSI; Group (I+II), PSI<30%. CI:
Kawamura E et al. Major complications in HCV-related cirrhosis 3885

Page 5

E, Andreu V, Real M, Escorsell A, Montanya X, Bosch J. CO
(2) wedged hepatic venography in the evaluation of portal
hypertension. Gut 2000; 46: 856-860
Abraldes JG, Tarantino I, Turnes J, Garcia-Pagan JC, Rodes
J, Bosch J. Hemodynamic response to pharmacological treat-
ment of portal hypertension and long-term prognosis of
cirrhosis. Hepatology 2003; 37: 902-908
Patch D, Nikolopoulou V, McCormick A, Dick R, Armonis
A , Wannamethee G, Burroughs A . Factors related to early
mortality after transjugular intrahepatic portosystemic shunt
for failed endoscopic therapy in acute variceal bleeding. J
Hepatol 1998; 28: 454-460
Shiomi S, Kuroki T, Kurai O, Kobayashi K, Ikeoka N, Monna
T, Ochi H. Portal circulation by technetium-99m pertechnetate
per-rectal portal scintigraphy. J Nucl Med 1988; 29: 460-465
Boldys H, Hartleb M, Rudzki K, Nowak A, Nowak S. Effect
of propranolol on portosystemic collateral circulation esti-
mated by per-rectal portal scintigraphy with technetium-99m
pertechnetate. J Hepatol 1995; 22: 173-178
Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Will-
iams R. Transection of the oesophagus for bleeding oesoph-
ageal varices. Br J Surg 1973; 60: 646-649
K usaka K , Harihara Y, Torzilli G, Kubota K, Takayama T,
Makuuchi M. Objective evaluation of liver consistency to es-
timate hepatic fibrosis and functional reserve for hepatectomy.
J Am Coll Surg 2000; 191: 47-53
Idezuki Y. General rules for recording endoscopic findings of
esophagogastric varices. Japanese Society for Portal Hypertension.
World J Surg 1995; 19: 420-422
Schlichting P, Christensen E, Andersen PK, Fauerholdt L, Juhl
E, Poulsen H, Tygstrup N. Prognostic factors in cirrhosis iden-
tified by Cox’s regression model. Hepatology 1983; 3: 889-895
Holford TR. Life tables with concomitant information. Bio-
metrics 1976; 32: 587-597
7
8
9
10
11
12
13
14
15
16Meijer K , Haagsma EB, Kok T, Schirm J, Smid WM, van der
Meer J. Natural history of hepatitis C in HIV-negative pa-
tients with congenital coagulation disorders. J Hepatol 1999;
31: 400-406
Urbain D, Jeghers O, Ham HR. Per-rectal portal scintigraphy:
comparison between technetium-99m, thallium-201, and io-
dine-123-HIPDM. J Nucl Med 1988; 29: 2020-2021
V orobioff J, Groszmann RJ, Picabea E, Gamen M, Villavicencio
R, Bordato J, Morel I, A udano M, Tanno H, Lerner E,
Passamonti M. Prognostic value of hepatic venous pressure
gradient measurements in alcoholic cirrhosis: a 10-year pro-
spective study. Gastroenterology 1996; 111: 701-709
Groszmann RJ, Bosch J, Grace ND, Conn HO, Garcia-Tsao
G, Navasa M, Alberts J, Rodes J, Fischer R, Bermann M. He-
modynamic events in a prospective randomized trial of pro-
pranolol versus placebo in the prevention of a first variceal
hemorrhage. Gastroenterology 1990; 99: 1401-1407
V illeneuve JP, Durantel D, Durantel S, Westland C, Xiong S,
Brosgart CL, Gibbs CS, Parvaz P, Werle B, Trepo C, Zoulim F.
Selection of a hepatitis B virus strain resistant to adefovir in a
liver transplantation patient. J Hepatol 2003; 39: 1085-1089
Rosen HR, Gretch D, Kaufman E, Quan S. Humoral immune
response to hepatitis C after liver transplantation: assessment
of a new recombinant immunoblot assay. Am J Gastroenterol
2000; 95: 2035-2039
Kiuchi T, Tanaka K, Ito T, Oike F, Ogura Y, Fujimoto Y, Ogawa
K. Small-for-size graft in living donor liver transplantation:
how far should we go? Liver Transpl 2003; 9: S29-35
Fevery J. Liver transplantation: problems and perspectives.
Hepatogastroenterology 1998; 45: 1039-1044
Bruix J, Castells A, Bosch J, Feu F, Fuster J, Garcia-Pagan JC,
Visa J, Bru C, Rodes J. Surgical resection of hepatocellular
carcinoma in cirrhotic patients: prognostic value of preopera-
tive portal pressure. Gastroenterology 1996; 111: 1018-1022
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Science Editor Guo SY Language Editor Elsevier HK
3886 ISSN 1007-9327 CN 14-1219/ R World J Gastroenterol July 7, 2005 Volume 11 Number 25