POSTERS
mediated immune response. These immune modulations, and
the peripheral T-cell depletion known to occur in cirrhosis,
may support development of autoimmunity. We therefore aimed
to investigate whether cirrhosis confers an increased risk of
autoimmune disease.
Methods: We used the Danish National Patient Registry (NPR)
to identify all Danish citizens diagnosed with cirrhosis in 1977–
2009. For each of them we sampled five gender- and age-matched
population controls. Cox regression was used to compare the rate
of rheumatoid arthritis, multiple sclerosis, or inflammatory bowel
disease development (identified through NPR) between cirrhosis
patients and controls.
Results: We included 38,394 cirrhotic patients. During 217,558 total
years of follow-up 442 of them developed rheumatoid arthritis
(N = 206), multiple sclerosis (N = 20), or inflammatory bowel disease
(N = 216). Cirrhosis patients were more likely than controls to
develop autoimmune disease (hazard ratio 1.66, 95% CI 1.49–1.85),
irrespective of gender. The association was strongest shortly after
cirrhosis was diagnosed and stable at a hazard ratio of about 1.45
from two years on after diagnosis of cirrhosis.
Conclusion: Liver cirrhosis associates with development of multiple
sclerosis, inflammatory bowel disease and/or rheumatoid arthritis.
This may indicate a general enhancement in susceptibility
for autoimmune phenomena in cirrhosis, and the underlying
mechanisms should be delineated.
628
A MULTICENTER, RANDOMIZED, DOUBLE-BLIND,
PLACEBO-CONTROLLED CLINICAL TRIAL TO EVALUTE THE
EFFICACY AND SAFETY OF TOLVAPTAN ON HYPONATREMIA
IN CHINESE CIRRHOTIC PATIENTS
J. Jia1 , H.F. Wang2 , J. Cheng3 , W. Ye4 , H. Ding5 , C. Deng6 , Z. Gai7 ,
G. Wang8 , H. Zhu9 , C. Chen10 , G. Gong11 , D. Zhang12 , Q. Xie13 ,
M. Wan14 , X. Cai15 , J. Li16 , R. Shi17 , Q. Mao18 , Y. Chen19 , J. Guo20 ,
J. Niu21 , H. Wang22 , M. Zeng23 . 1 Liver Research Center, Beijing
Friendship Hospital, 2 Center for Liver Failure Treatment and Reasearch,
302 Military Hospital of China, 3 Center of Liver Diseases, Beijing Ditan
Hospital, Beijing, 4 Dept of Infection, The First Affiliated Hospital of
Zhejiang University College of Medicine, Hangzhou, 5 Dept of Digestion,
Beijing Youan Hospital, Capital University Hospital, Beijing, 6 Dept
of Infectious Diseases, Hospital Affiliated to Luzhou Medical College,
Luzhou, 7 Dept of Infectious Diseases, Infectious Disease Hospital of
Jinan, Jinan, 8 Dept of Infectious Diseases, Center for Liver Diseases,
Peking University First Hospital, Beijing, 9 Dept of Digestive Internal
Medicine, Subei People’s Hospital of Jiangsu Province, Yangzhou,
10
Center of Liver Disease, 85th Military Hospital, Shanghai, 11 Dept of
Infectious Diseases, The Second Xiangya Hospital of Central South
University, Changsha, 12 Dept of Infectious Diseases, The Second
Affiliated Hospital Chongqing Medical University, Chongqing, 13 Dept
of Infectious Diseases, Ruijin Hospital of Shanghai Jiaotong University
School of Medicine, 14 Dept of Infectious Diseases, Changhai Hospital
of Shanghai, 15 Dept of Liver Disease, Changzheng Hospital, Shanghai,
16
Dept of Infectious Diseases, 17 Dept of Digestion, The People’s Hospital
of Jiangsu Province, Nanjing, 18 Dept of Infectious Diseases, Chongqing
Southwest Hospital, Chongqing, 19 Dept of Infectious Diseases, The First
Affiliated Hospital of Wenzhou Medical College, Wenzhou, 20 Dept of
Digestive Internal Medicine, Wuxi People’s Hospital, Wuxi, 21 Dept
of Hepatic-Biliary-Pancreatic Medicine, The First Hospital of Jilin
University, Changchun, 22 Institute of Liver Disease, Peking University
People’s Hospital, Beijing, 23 Dept of Digestive Internal Medicine, Renji
Hospital, Shanghai Jiaotong University School of Medicine, Shanghai,
China
E-mail: jia_jd@ccum.edu.cn
Background and Aims: Tolvaptan has been shown effective in
treating hyponatremia in previous studies. However, its efficacy
and safety has not been confirmed in Asian patients. Therefore,
Journal of Hepatology 2012 vol. 56 | S225–S388
a clinical trial of tolvaptan was performed in Chinese cirrhotic
patients in present study.
Methods: Patients were randomized to receive placebo or tolvaptan
with initial dose of 15 mg/day, and then titrated to 30 or 60 mg/day
based on serum sodium concentrations. The primary endpoint was
the average daily changes of serum sodium from baseline to day 4
and day 7. The secondary endpoints included:
1. change of serum sodium from baseline;
2. percentage of patients with normalized serum sodium;
3. percentage of patients requiring fluid restriction;
4. urine output on day 1;
5. fluid balance;
6. change of abdominal circumference and body weight from
baseline;
7. change of lower extremity edema/ascites on day 7.
Results: Compared with placebo, tolvaptan caused greater increase
in average daily change in serum sodium from baseline to day 4
(4.12±2.59 vs. 0.28±2.46 mmol/L, p < 0.0001) and from baseline
to day 7 (4.86±2.86 vs. 0.62±3.09 mmol/L, p < 0.0001), For the
secondary endpoints, tolvaptan resulted in higher increases in
absolute plasma sodium concentrations than placebo and the
change was maintained during the study drug administration.
Within 7 days after cessation of dosing, serum sodium
concentrations in tolvaptan-treated patients declined to levels
similar to placebo-treated patients. Tolvaptan was well tolerated in
most patients. The most common adverse events occurring during
the study in the tolvaptan group were dry mouth and thirst.
Conclusions: Tolvaptan is effective for hyponatremia in Chinese
cirrhotic patients during the drug administration period, with an
acceptable safety profile.
629
CEREBRAL OEDEMA IS RARE IN ACUTE-ON-CHRONIC LIVER
FAILURE (AOCLF)
D. Joshi1 , A. Patel1 , J. O’Grady1 , E. Stern1 , D. Shawcross1 , S. Connor2 ,
C. Willars1 , W. Bernal1 , J. Wendon1 , G. Auzinger1 . 1 Institute of Liver
Studies, 2 Neuro-Radiology, King’s College Hospital, London, UK
E-mail: d.joshi@nhs.net
Introduction: AoCLF has a rapid disease course associated with
significant mortality. Hepatic encephalopathy (HE) is common
associated with hyperammonemia, systemic inflammation and
hyponatremia. The incidence of cerebral oedema in AoCLF is
unknown.
Aim: To describe the incidence of cerebral oedema in AoCLF adult
patients admitted to the liver intensive treatment unit (January
2005-January 2011).
Methods: AoCLF was defined according to Sarin et al (2009).
Arterial ammonia (NH3), MELD, UKELD, and SOFA scores were
collated (results median with ranges). Patients who had undergone
neuro-imaging were identified. Scans were reported by consultant
neuro-radiologists.
Results: 1008 patients with chronic liver disease (CLD) were
admitted, 173 patients underwent neuro-imaging. 81 (48 male)
fulfilled criteria for AoCLF. Variceal bleeding (30%) and sepsis (31%)
were the commonsest precipitants of AoCLF. Compared to the CLD,
AoCLF patients were younger (50, 24–71 vs 59, 30–74, p = 0.001),
NH3 (143, 40–305 vs 111, 28–315), grade of HE (3, 1–4 vs 1, 0–4),
MELD (25, 8–40 vs 15, 6–34), SOFA (11, 2–17 vs 4, 0–14), UKELD (63,
50–75 vs 55, 44–73) and SIRS score (2, 1–3 vs 1, 0–3) were higher
(p < 0.0001 for all). Serum sodium was lower in AoCLF group (132,
118–154 vs 136, 120–146, p < 0.0001). HE (≥ grade 3) occurred in
66% of AoCLF patients vs13% CLD (p < 0.0001). In those with neuro-
imaging, 26% normal, 26% demonstrated increased cerebral atrophy
for age, 15% small vessel disease and 10% intra-cranial haemorrhage.
Cerebral oedema was seen in 2 patients with AoCLF, 1 post TIPSS
(NH3 289 mmol/L) and 1 with septic shock (NH3 268 mmol/L). 72
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