Clinical and Molecular Hepatology

"Bleeding"

Original Article

Liver fibrosis, cirrhosis, and portal hypertension

Alcohol associated liver cirrhotics have higher mortality after index hospitalization: Long-term data of 5,138 patients: Priyanka Jain, Saggere Muralikrishna Shasthry, Ashok Kumar Choudhury, Rakhi Maiwall, Guresh Kumar, Ankit Bharadwaj, Vinod Arora, Rajan Vijayaraghavan, Ankur Jindal, Manoj Kumar Sharma, Vikram Bhatia, Shiv Kumar Sarin; Clin Mol Hepatol 2021;27(1):175-185.
Published online December 3, 2020; DOI: https://doi.org/10.3350/cmh.2020.0068

Abstract
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Background/Aims
Liver cirrhosis is an important cause of morbidity and mortality globally. Every episode of decompensation and hospitalization reduces survival. We studied the clinical profile and long-term outcomes comparing alcohol-related cirrhosis (ALC) and non-ALC.

Methods
Cirrhosis patients at index hospitalisation (from January 2010 to June 2017), with ≥1 year follow-up were included.

Results
Five thousand and one hundred thirty-eight cirrhosis patients (age, 49.8±14.6 years; male, 79.5%; alcohol, 39.5%; Child-A:B:C, 11.7%:41.6%:46.8%) from their index hospitalization were analysed. The median time from diagnosis of cirrhosis to index hospitalization was 2 years (0.2–10). One thousand and seven hundred seven patients (33.2%) died within a year; 1,248 (24.3%) during index hospitalization. 59.5% (2,316/3,890) of the survivors, required at least one readmission, with additional mortality of 19.8% (459/2,316). ALC compared to non-ALC were more often (P<0.001) male (97.7% vs. 67.7%), younger (40–50 group, 36.2% vs. 20.2%; P<0.001) with higher liver related complications at baseline, (P<0.001 for each), sepsis: 20.3% vs. 14.9%; ascites: 82.2% vs. 65.9%; spontaneous bacterial peritonitis: 21.8% vs. 15.7%; hepatic encephalopathy: 41.0% vs. 25.0%; acute variceal bleeding: 32.0% vs. 23.7%; and acute kidney injury 30.5% vs. 19.6%. ALC patients had higher Child-Pugh (10.6±2.0 vs. 9.0±2.3), model for end-stage liver-disease scores (21.49±8.47 vs. 16.85±7.79), and higher mortality (42.3% vs. 27.3%, P<0.001) compared to non-ALC.

Conclusions
One-third of cirrhosis patients die in index hospitalization. 60% of the survivors require at least one rehospitalization within a year. ALC patients present with higher morbidity and mortality and at a younger age.

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Editorial

Acute liver injury and Acute liver failure

Acute-on-chronic liver failure: A predictor of poor prognosis in patients with variceal bleeding or a risk factor for variceal bleeding?: Nae-Yun Heo; Clin Mol Hepatol 2020;26(4):487-488.
Published online October 1, 2020; DOI: https://doi.org/10.3350/cmh.2020.0209

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Clinical and Molecular Hepatology.2022; 28(3): 540. CrossRef

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Original Articles

Acute liver injury and Acute liver failure

Acute-on-chronic liver failure as a major predictive factor for mortality in patients with variceal bleeding: Jongbeom Shin, Jung Hwan Yu, Young-Joo Jin, Hyung Joon Yim, Young Kul Jung, Jin Mo Yang, Do Seon Song, Young Seok Kim, Sang Gyune Kim, Dong Joon Kim, Ki Tae Suk, Eileen L. Yoon, Sang Soo Lee, Chang Wook Kim, Hee Yeon Kim, Jae Young Jang, Soung Won Jeong, on Behalf of the Korean Acute-onChronic Liver Failure (KACLiF) Study Group; Clin Mol Hepatol 2020;26(4):540-553.
Published online September 17, 2020; DOI: https://doi.org/10.3350/cmh.2020.0034

Background/Aims
This study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients.
Methods
This study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium.
Results
Among a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (P<0.001), and patients with higher ACLF grades had a lower OS rate (P<0.001). The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score was identified as a significant prognostic factor in patients hospitalized with variceal bleeding (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.30–1.50; P<0.001), even in ACLF patients with variceal bleeding (HR, 1.32; 95% CI, 1.19–1.46, P<0.001). Concerning the prediction of the mortality risk at 28- and 90-day using CLIF-SOFA scores, c-statistics were 0.895 (95% CI, 0.829–0.962) and 0.897 (95% CI, 0.842–0.951), respectively, and the optimal cut-off values were 6.5 and 6.5, respectively.
Conclusions
In cirrhotic patients hospitalized with variceal bleeding, the prognosis was poor when accompanied by ACLF, especially depending upon CLIF-SOFA score. CLIF-SOFA model well predicted the 28-day or 90-day mortality for cirrhotic patients who experienced variceal bleeding.

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Liver fibrosis, cirrhosis, and portal hypertension

Emergency endoscopic variceal ligation in cirrhotic patients with blood clots in the stomach but no active bleeding or stigmata increases the risk of rebleeding: Su Jin Kim, Cheol Woong Choi, Dae Hwan Kang, Hyung Wook Kim, Su Bum Park, Young Mi Hong, Ki Tae Yoon, Mong Cho, Hyung Seok Nam, SM Bakhtiar UI Islam; Clin Mol Hepatol 2016;22(4):466-476.
Published online December 25, 2016; DOI: https://doi.org/10.3350/cmh.2016.0063

Abstract
PDF

Background/Aims
This study aimed to evaluate the efficacy and safety of emergency variceal ligation for the prevention of rebleeding in cirrhotic patients who are found on initial endoscopy to have blood clots in the stomach but no actively bleeding esophageal and gastric varices or stigmata.
Methods
This study included 28 cirrhotic patients who underwent emergency prophylactic EVL and 41 who underwent an elective intervention between January 2009 and June 2014. Clinical outcomes were analyzed, including the rebleeding, 6-week mortality, and rebleeding-free survival rates.
Results
The rebleeding rate was higher in the emergency than in the elective group (28.6% vs. 7.3%, P=0.041). Multivariate analysis showed that emergency prophylactic EVL (odds ratio [OR] = 7.4, 95% confidence interval [CI]=1.634.8, P=0.012) and Child-Pugh score C (OR=10.6, 95% CI=1.4-80.8, P=0.022) were associated with rebleeding. In the emergency group, the gastric varices were associated with rebleeding (OR=12.0, 95% CI=1.7-83.5, P=0.012).
Conclusions
Emergency EVL may be associated with variceal rebleeding when blood clots are present in the stomach without active esophageal and gastric variceal bleeding or stigmata. Elective intervention should be considered as a safer strategy for preventing variceal rebleeding in this situation.

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Liver fibrosis, cirrhosis, and portal hypertension

The comparison of esophageal variceal ligation plus propranolol versus propranolol alone for the primary prophylaxis of esophageal variceal bleeding: Dongmo Je, Yong-Han Paik, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Byung Chul Yoo; Clin Mol Hepatol 2014;20(3):283-290.
Published online September 25, 2014; DOI: https://doi.org/10.3350/cmh.2014.20.3.283

Abstract
PDF

Background/Aims

To investigate the efficacy and longterm outcome of esophageal variceal ligation (EVL) plus propranolol in comparison with propranolol alone for the primary prophylaxis of esophageal variceal bleeding.

Methods

A total of 504 patients were retrospectively enrolled in this study. 330 patients were in propranolol group (Gr1) and 174 patients were in EVL plus propranolol group (Gr2). The endpoints of this study were esophageal variceal bleeding and mortality. Association analyses were performed to evaluate bleeding and mortality between Gr1 and Gr2.

Results

EVL was more applied in patients with high risk, such as large-sized varices (F2 or F3) or positive red color signs. Total 38 patients had bleeds, 32 in Gr1 and 6 in Gr2. The cumulative probability of bleeding at 120 months was 13% in Gr1 versus 4% in Gr2 (P=0.04). The predictive factors of variceal bleeding were red color signs (OR 2.962, P=0.007) and the method of propranolol plus EVL (OR 0.160, P=0.000). 20 patients died in Gr1 and 12 in Gr2. Mortality rates are similar in the two groups compared, 6.7% in Gr1 and 6.9% in Gr2. The cumulative probability of mortality at 120 months was not significantly different in the two groups (7% in Gr1, 12% in Gr2, P=0.798). The prognostic factors for mortality were age over 50 (OR 5.496, P=0.002), Child-Pugh class B (OR 3.979, P=0.001), and Child-Pugh class C (OR 10.861, P=0.000).

Conclusions

EVL plus propranolol is more effective than propranolol alone in the prevention of the first variceal bleeding in patients with liver cirrhosis.

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Gautam Ray
Indian Journal of Gastroenterology.2019; 38(1): 69. CrossRef
Liver volume index predicts the risk of esophageal variceal hemorrhage in cirrhotic patients on propranolol prophylaxis
Beom Hee Kim, Jung Wha Chung, Chung Seop Lee, Eun Sun Jang, Sook-Hyang Jeong, Nayoung Kim, Jin-Wook Kim
The Korean Journal of Internal Medicine.2019; 34(6): 1233. CrossRef
Carvedilol for reducing portal pressure in primary prophylaxis of variceal bleeding: a dose‐response study
R. Schwarzer, D. Kivaranovic, R. Paternostro, M. Mandorfer, T. Reiberger, M. Trauner, M. Peck‐Radosavljevic, A. Ferlitsch
Alimentary Pharmacology & Therapeutics.2018; 47(8): 1162. CrossRef
Small Esophageal Varices in Patients with Cirrhosis—Should We Treat Them?
Thomas Reiberger, Theresa Bucsics, Rafael Paternostro, Nikolaus Pfisterer, Florian Riedl, Mattias Mandorfer
Current Hepatology Reports.2018; 17(4): 301. CrossRef
Rifaximin and Propranolol Combination Therapy Is More Effective than Propranolol Monotherapy for the Reduction of Portal Pressure: An Open Randomized Controlled Pilot Study
Yoo Li Lim, Moon Young Kim, Yoon Ok Jang, Soon Koo Baik, Sang Ok Kwon
Gut and Liver.2017; 11(5): 702. CrossRef
Changes in Cardiac Varices and Their Clinical Significance after Eradication of Esophageal Varices by Band Ligation
Seung Woon Park, Yeon Seok Seo, Han Ah Lee, Sang Jung Park, Tae Hyung Kim, Jae Min Lee, Sang Jun Suh, Hyuk Soon Choi, Eun Sun Kim, Bora Keum, Young Kul Jung, Ji Hoon Kim, Hyonggin An, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Hong Sik Lee, Hoon Jai Ch
Canadian Journal of Gastroenterology and Hepatology.2016; 2016: 1. CrossRef

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Liver fibrosis, cirrhosis, and portal hypertension

Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data: Moon Young Kim, Soon Ho Um, Soon Koo Baik, Yeon Seok Seo, Soo Young Park, Jung Il Lee, Jin Woo Lee, Gab Jin Cheon, Joo Hyun Sohn, Tae Yeob Kim, Young Suk Lim, Tae Hyo Kim, Tae Hee Lee, Sung Jae Park, Seung Ha Park, Jin Dong Kim, Sang Young Han, Chang Soo Choi, Eun Young Cho, Dong Joon Kim, Jae Seok Hwang, Byoung Kuk Jang, June Sung Lee, Sang Gyune Kim, Young Seok Kim, So Young Kwon, Won Hyeok Choe, Chang Hyeong Lee, Byung Seok Kim, Jae Young Jang, Soung Won Jeong, Byung Ho Kim, Jae Jun Shim, Yong Kyun Cho, Moon Soo Koh, Hyun Woong Lee; Korean J Hepatol 2013;19(1):36-44.
Published online March 25, 2013; DOI: https://doi.org/10.3350/cmh.2013.19.1.36

Abstract
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Background/Aims

While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.

Methods

The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.

Results

The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).

Conclusions

The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.

Citations

Citations to this article as recorded by

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Effect of Transjugular Intrahepatic Portosystemic Shunt for Variceal bleeding in Hepatocellular Carcinoma Patients with Portal Vein Thrombosis: Woo Jin Chung, M.D., Byung Kuk Jang, M.D., Kyung Sik Park, M.D., Kwang Bum Cho, M.D., Jae Seok Hwang, M.D., Sung Hun Ahn, M.D., Yong Hoon Kim, M.D.1, Young Hwan Kim, M.D.2 and Yong Ju Kim, M.D.3; Korean J Hepatol 2005;11(2):157-163.

Abstract
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Background/Aims
Transjugular Intrahepatic Portosystemic Shunt (TIPS) is commonly used in patients with variceal bleeding. However, this procedure is contraindicated in hepatocellular carcinoma patients with portal vein thrombosis. This study was done to evaluate the effect of TIPS in those patients with variceal bleeding. Methods: Between 1997 and 2004, six hepatocellular carcinoma (HCC) patients with portal vein thrombosis were enrolled in this study due to their variceal bleeding. All the patients underwent TIPS placement to treat the variceal bleeding that had not responded to endoscopic treatment. Effective shunt creation was assessed by the decrease of the portal pressure gradient (less than 12 mmHg) or if good patency and flow were seen on a doppler examination. Results: Shunts were successfully created in all the patients and the bleeding was immediately controlled in the active bleeding cases. The bleeding was caused by esophageal varices in one patient and, by gastric varices in five patients. The HCC types were diffuse or massive in five patients, and a single nodule was present in one patient. All the patients had portal vein thrombosis. Rebleeding was noted in two patients at 10 days and 3 months, respectively, due to the shunt occlusion. Hepatic encephalopathy was noted in two patients. The causes of death were hepatorenal syndrome after 2 weeks in one patient, bleeding due to portal hypertensive gastropathy after 3 weeks in another, and cancer progression after 4 months in third patient. Conclusions: For HCC patients with portal vein thrombosis, TIPS can be an effective treatment modality if uncontrolled variceal bleeding presents when using endoscopic hemostasis or pharmacologic therapy. However, further studies are needed. (Korean J Hepatol 2005;11: 157-163)

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Effect of Low-dose, Enteric Coated Aspirin on Gastrointestinal Bleeding in Patients with Coronary Artery Disease: Chang Kyu Choi , Na Young Kim , Jin Woo Choi , Young Soo Park , Jin Wook Kim , Sook Hyang Jeong , Dong Ho Lee , Young Seok Cho , Tae Jin Youn , Woo Young Chung , In Ho Chae , Dong Ju Choi; Korean J Hepatol 2008;12(2):99-104.

Abstract
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Background/Aims
This study was performed to determine whether low-dose aspirin and/or clopidogrel can induce gastrointestinal bleeding and gastroduodenal mucosal injury. Methods: A total of 387 patients who underwent coronary angiography at Seoul National University Bundang Hospital were assigned to one of three antiplatelet treatment groups: (1) control, (2) 100-mg enteric coated aspirin, and (3) 100-mg enteric coated aspirin plus clopidogrel. The incidences of gastroduodenal mucosal injury and gastrointestinal bleeding were prospectively evaluated, and risk factors for gastrointestinal bleeding were analyzed. Results: The rate of gastroduodenal mucosal injury was higher in the aspirin-plus-clopidogrel group than in the aspirin group (p=0.012), and higher in the aspirin group than in the control group (p=0.049). The rate of gastrointestinal bleeding was significantly higher in the aspirin-plus-clopidogrel group (9.4%) than in the control group (2.4%, p=0.048). The risk factors for gastrointestinal bleeding were older age (≥60 years) and the presence of at least two comorbid disorders. Conclusions: Low-dose enteric coated aspirin was found to be safe in patients with coronary artery disease, but the addition of clopidogrel increased the rate of gastrointestinal bleeding. Combined clopidogrel and aspirin should be used with caution in older patients having at least two comorbid conditions.

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A Prospective Study Comparing the Efficacy of Early Administration of Terlipressin and Somatostatin for the Control of Acute Variceal Bleeding in Patients with Cirrhosis: Yeon Seok Seo, M.D., Soon Ho Um, M.D., Jong Jin Hyun, M.D., Youn Ho Kim, M.D., Sanghoon Park, M.D., Bo Ra Keum, M.D., Yong Sik Kim, M.D., Yoon Tae Jeen, M.D., Hong Sik Lee, M.D., Hoon Jai Chun, M.D., Sang Woo Lee, M.D., Jai Hyun Choi, M.D., Chang Duck Kim, M.D., and Ho Sang Ryu, M.D.; Korean J Hepatol 2006;12(3):373-384.

Abstract
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Background/Aims
Terlipressin and somatostatin decrease portal venous pressure and they are used for the treatment of variceal bleeding. However, only a few studies have compared the efficacy of these drugs in combination with other procedures for hemostasis. Therefore, we performed a prospective study to compare the efficacy of terlipressin and somatostatin for controlling acute variceal bleeding when used in combination with other procedures for hemostasis. Methods: A total of 98 patients, who presented with variceal bleeding from September 2003 to May 2005, were randomly divided into the somatostatin group or terlipressin group. We compared the 5-day failure rate (defined as failure to control bleeding, rebleeding or death within 5 days of admission) and the 6-week mortality. The prognostic factors for 5-day failure and 6-week mortality were also evaluated. Results: There were no differences in baseline characteristics between the two groups. The overall 5-day failure rate and the cumulative 6-week mortality were 16.3% and 15.8%, respectively. The five-day failure rate and the cumulative 6-week mortality were not significantly different between the somatostatin and terlipressin groups. Hepatocellular carcinoma, the baseline serum creatinine level and endoscopic treatment for hemostasis were the significant predictors of 5-day failure; the baseline serum creatinine level was the predictor of 6-week mortality. Conclusions: Both somatostatin and terlipressin were effective and showed comparable efficacy for the control of the acute variceal bleeding in the setting of a combined therapeutic approach. The baseline serum creatinine level may be a significant predictor for patient failure at 5 days and the 6-week mortality.

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Comparison of Terlipressin and Octreotide with Variceal Ligation for Controlling Acute Esophageal Variceal Bleeding - a Randomized Prospective Study: Sung Bum Cho , Kang Jin Park , Jung Soo Lee , Wan Sik Lee , Chang Hwan Park , Young Eun Joo , Hyun Soo Kim , Sung Kyu Choi , Jong Sun Rew , Sei Jong Kim; Korean J Hepatol 2006;12(3):385-393.

Abstract
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Background/Aims: Terlipressin and octreotide had been used to control acute variceal bleeding and to prevent early rebleeding after endoscopic hemostasis. We compared the efficacy and safety of terlipressin and octreotide combined with endoscopic variceal ligation (EVL) for the treatment of acute esophageal variceal bleeding and we evaluated their clinical significance as related to rebleeding. Methods: The eighty eight cirrhotic patients were randomized to the terlipressin group (n=43; 2 mg i.v. initially and 1 mg i.v. at every 4 hours for 3 days) or the octreotide group (n=45; continuous infusion of 25 μg/h for 5 days) combined with EVL for the treatment of acute esophageal variceal bleeding. Results: The initial hemostasis rates were 98% (42/43 cases) in the terlipressin group and 96% (43/45 cases) in the octreotide group. The 5-day and 42-day rebleeding rates were 12% (5/43 cases) and 28% (12/43 cases), respectively, in the terlipressin group and 9% (4/45 cases) and 24% (11/45 cases), respectively, in the octreotide group. No significant difference was demonstrated between the terlipressin and octreotide groups. The mortality at 42 days was similar in both group, but a high mortality rate (48%) was shown to be related to 42-day rebleeding. The risk factors related to 42-day rebleeding were Child-Pugh class C (aOR=30.2, 95% CI=7.7-117.9), ascites above grade II (aOR=6.6, 95% CI=2.2-19.2) and advanced hepatocellular carcinoma (aOR=4.6, 95% CI=1.1-18.9). Conclusions: Comparing terlipressin and octreotide combined with EVL showed them to be equally safe and effective therapeutic agents in patients with acute esophageal variceal bleeding. The high risk factors related to early rebleeding were poor liver function and advanced hepatocellular carcinoma.

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Prospective Randomized Trial of Intravenous Ciprofloxacin for Prevention of Bacterial Infection in Cirrhotic Patients with Esophageal Variceal Bleeding: Sung Noh Hong, Beom Jin Kim, Sun Young Lee, Choon Young Lee, Min Kyu Ryu, Moon Seok Choi, Joon Hyoek Lee, Poong Lyul Rhee, Kwang Cheol Koh, Jae J Kim, Seung Woon Paik, Jong Chul Rhee, and Kyoo Wan Choi; Korean J Hepatol 2002;8(3):288-296.

Abstract
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Background/Aims
In cirrhotic patients with esophageal variceal bleeding, bacterial infections are a frequent complication. Oral antibiotic prophylaxis decreases the incidence of bacterial infections. The administration of oral antibiotics, however, may be difficult in some cirrhotic patients with active bleeding.The purpose of this study was to assess the efficacy of prophylactic intravenous antibiotics for the prevention of bacterial infections in cirrhotic patients with esophageal variceal bleeding. Methods: From December 1998 to September 2001, a total of 40 consecutive cirrhotic patients with Child-Pugh class B or C were enrolled after emergent endoscopic esophageal variceal ligation (EVL) was taken because of esophageal variceal bleeding. Enrolled patients were randomized into a treatment group and a control group. The treatment group (n=20) received the intravenous ciprofloxacin 200mg IV q 12 hours for 3 days while the control group(n=20) didn,t. Results: Bacterial infection developed in nine patients (45%) of the control group and only two patients (10%) in the treatment group. The incidence of bacterial infections was significantly lower in the treatment group than the control group (p<0.005). The hospital cost and length of hospital stay decreased in the treatment group compared with the control group (p<0.001). There were no differences in the hospital course and mortality within 30 days between the two groups. Conclusions: In cirrhotic patients with variceal bleeding and with Child-Pugh class B or C, the use of intravenous ciprofloxacin for 3 days after EVL was not only effective in the prevention of bacterial infections but also cost-effective. (Korean J Hepatol 2002;8:288-296)

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Hepatology Elsewhere

The Korean Journal of Prevention of Variceal Bleeding and Measurement of Hepatic Vein Pressure Gradient: Kwang Hee Youn , Dong Joon Kim; Korean J Hepatol 2006;12(3):464-468.

Abstract
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Objective
s: A reduction in hepatic venous pressure gradient (HVPG) of ≥20% of baseline or to ≤12 mmHg (responders) is associated with a reduced risk of first variceal bleeding. The aim of this study was to evaluate whether this protective effect is maintained in the long term and if it extends to other portal hypertension complications. Methods: Seventyone cirrhotic patients with esophageal varices and without previous variceal bleeding who entered into a program of prophylactic pharmacological therapy and were followed for up to 8 yr were evaluated. All had two separate HVPG measurements, at baseline and after pharmacological therapy with propranolol± isosorbide mononitrate. Results: Forty-six patients were nonresponders and 25 were responders. Eightyear cumulative probability of being free of first variceal bleeding was higher in responders than in nonresponders (90% vs 45%, p=0.026). The lack of hemodynamic response and low platelet count were the only independent predictors of first variceal bleeding. Additionally, reduction of HVPG was independently associated with a decreased risk of spontaneous bacterial peritonitis (SBP) or bacteremia. No significant differences in the development of ascites, hepatic encephalopathy, or survival were observed. Conclusions: The hemodynamic response in cirrhotic patients is associated with a sustained reduction in the risk of first variceal bleeding over a long-term follow-up. Reduction of HVPG also correlate with a reduced risk of SBP or bacteremia. [Abstract reproduced by permisson of Am J Gastroenterol 2006;101:506-512]

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Original Articles

Comparison of Predictive Factors Related to the Mortality and Rebleeding Caused by Variceal Bleeding: Child-Pugh Score, MELD Score, and Rockall Score: Ja Young Lee, M.D., Jin Heon Lee, M.D., Soo Jin Kim, M.D., Dae Rho Choi, M.D., Kyung Ho Kim, M.D., Yong Bum Kim, M.D., Hak Yang Kim, M.D. and Jae Young Yoo, M.D.; Korean J Hepatol 2002;8(4):458-464.

Abstract
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Background/Aims
The first episode of variceal bleeding is one of the most frequent causes of death in patients with liver cirrhosis. The Child-Pugh(CP) scoring system has been widely accepted for prognostic assessment. Recently, MELD has been known to be better than the CP scoring system for predicting mortality in patients with end-stage liver diseases. The Rockall risk scoring system was developed to predict the outcome of upper GI bleeding including variceal bleeding. The aim of this study was to investigate the mortality rate of first variceal bleeding and the predictability of each scoring system. Methods: We evaluated the 6-week mortality rate, rebleeding rate, and 1-year mortality rate of all the 136 patients with acute variceal bleeding without previous episode of hemorrhage between January 1, 1998 and December 31, 2000. The CP score, MELD score, and Rockall score were estimated and analyzed. Results: Among 136 patients, 35 patients with hepatoma and 8 patients with follow-up loss were excluded. Six-week mortality rate, 1-year mortality rate, and rebleeding rate of first variceal bleeding were 24.7%, 35.5%, and 12.9%, respectively. The c-statistics of CP, MELD, and Rockall score for predicting 6-week mortality rate were 0.809 (p<0.001, 95% CI, 0.720-0.898), 0.804 (p<0.001, 95% CI, 0.696-0.911), 0.787 (p<0.001, 95% CI, 0.683-0.890), respectively. For 1-year mortality rate, c-statistics were 0.765 (p<0.005, 95% CI, 0.665-0.865), 0.780 (p<0.005, 95% CI, 0.676-0.883), 0.730 (p<0.01, 95% CI, 0.627-0.834), respectively. Conclusion: The CP, MELD, and Rockall scores were reliable measures of mortality risk in patients with first variceal bleeding. The CP classification is useful in its easy applicability. (Korean J Hepatol 2002;8:458-464)

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Usefulness of ΔMELD/month for Prediction of the Mortality in the First Episode of Variceal Bleeding Patients with Liver Cirrhosis: Comparison with CTP, MELD score and ΔCTP/month: Won Ki Bae, M.D., June Sung Lee, M.D., Nam Hoon Kim, M.D., Kyung Ah Kim, M.D., Young Soo Moon, M.D., Min Kyung Oh, Ph.D.1; Korean J Hepatol 2007;13(1):51-60.

Abstract
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Background/Aims
There are many models for predicting prognosis of liver cirrhosis including Child Turcotte Pugh (CTP), the model for end-stage liver disease (MELD) score and its changes over time (ΔCTP and ΔMELD/month). We investigated the ability of these models to predict the mortality of liver cirrhosis patients with the first episode of variceal bleeding and which model can be usefully applied in practice.
Methods
Seventy-one liver cirrhosis patients hospitalized for the first episode of esophageal variceal bleeding were retrospectively analyzed. The predictive power of initial CTP, MELD score, ΔCTP and ΔMELD/month was compared through c-statistics and multiple logistic regression. Results: All of the prognostic predictors measured higher in patients who survived than in those who died. The area under the receiver operating characteristic (ROC) curve for ΔMELD/month in 6 months was 1, a higher value than 0.81 for initial CTP, 0.75 for initial MELD, and 0.84 for ΔCTP/month; the area of ΔMELD/month in 12 months was 0.81, also showing a higher value than others. ΔMELD/month > 0.27 was a strong significant prognostic predictor in 6 (odds ratio: 40.1, p=0.001) and 12 months (odds ratio: 14.1, p<0.001). Only the ΔMELD/month was an independent prognostic predictor with a risk ratio of 1.604 (95% CI: 1.119-2.302, p=0.01) in 6 months and 1.627 (95% CI: 1.294-2.047, p<0.001) in 12 months. Conclusions: The ΔMELD/month is superior to initial CTP, MELD and ΔCTP/month to predict 6 and 12 months mortality in liver cirrhosis patients with the first episode of variceal bleeding. (Korean J Hepatol 2007;13:51-60)

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Endoscopic Variceal Ligation plus Octreotide versus Variceal Ligation Alone for the Prevention of Early Rebleeding from Esophageal Varices: Gyu Hyun Lee, M.D., Sung Won Cho, M.D., Heon Jong Kim, M.D. Kwang Hyun Ko, M.D., Young Yun Ko, M.D., Jun Ho Ko, M.D. Ho Dong Kim, M.D., Kwang Jae Lee, M.D., Ki Baik Hahm, M.D. and Jin Hong Kim, M.D.; Korean J Hepatol 1999;5(4):299-305.

Abstract
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Background/Aims
Endoscopic variceal ligation (EVL) has been effective modality for esophageal variceal bleeding, but recurrent bleeding occurs 20 to 40% of patients. So there has been an increased interest in the use of vasoactive drugs to lower portal hypertension and help control variceal bleeding before and after endoscopy. We investigated the efficacy of octreotide (OCT) infusion as an adjunct to EVL for preventing early rebleeding from varices. Methods: From Jan. 1997 to Feb. 1999, fifty four patients with endoscopically documented esophageal variceal bleeding were included. The patients were randomly treated by EVL alone (EVL group, n=30) or EVL plus octreotide (EVL+OCT group, n=24). We evaluated the 5-day and 6-week rebleeding rate and 6-week mortality. Results: Baseline characteristics were similar in two group but hospital stay (p=0.028) and units of transfused blood (p=0.043) were significantly less in EVL+OCT group. There were no significant differences on 5-day rebleeding rate (EVL group; 7%, EVL+OCT group; 0%) and 6-week rebleeding rate (EVL group; 20%, EVL+OCT group; 4%). Conclusions: The combined therapy did not decrease early rebleeding and mortality, but it was superior to EVL alone in hospital course such as requirement of transfusion and duration of hospitalization. (Korean J Hepatol 1999;5:299－305)

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N-Butyl-2-Cyanoacrylate (Histoacryl) in the Treatment of Esophageal Variceal Bleeding ; Comparison with Band Ligation: Gyu Hyun Lee, M.D., Yong Jun Shin, M.D, Young Yun Ko, M.D. Jun Ho Ko, M.D., Ho Dong Kim, M.D., Byeong Moo Yoo, M.D. Kwang Jae Lee, M.D., Young Soo Kim, M.D., Ki Baik Hahm, M.D. Jin Hong Kim, M.D. and Sung Won Cho, M.D.; Korean J Hepatol 1999;5(4):306-313.

Abstract
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Background
/Aim: Endoscopic sclerotherapy and band ligation have been well documented beneficial therapeutic options of esophageal variceal bleeding. But acute variceal bleeding is refractory to sclerotherapy in upto one-third of patients, and rebleeding occurs in 30% to 50%. Recently alternative endoscopic modality, N-butyl-2-cyanoacrylate (Histoacryl) injection is performed in intravariceal sclerotherapy but its efficacy and safty are not clearly established. We evaluated the efficacy of Histoacryl on esophageal variceal bleeding and compared with that of endoscopic band ligation in the present study. Materials/Methods: From March 1994 to March 1998, ninety seven patients with endoscopically documented esophageal variceal bleeding were enrolled. Histoacryl injection (Histoacryl group, n=33) or endoscopic band ligation (EVL group, n=64) was done for esophageal variceal bleeding. We evaluated the rebleeding rate and in-hospital mortality in both groups. Results: Baseline characteristics were similar but active bleeding on first endoscopic session was significantly higher in Histoacryl group (Histoacryl group; 90.7%, EVL group; 26.6%, p=0.002). Successful hemostasis was done at 87.9% in Histoacryl group, 95.3% in EVL group (not significant). There were no significant differences on early rebleeding rate (18.2% vs 23.4%), late rebleeding rate (39.4% vs 37.5%) and in-hospital mortality (24.2% vs 15.6%) between Histoacryl group and EVL group. There were no technique-related fatal complications at Histoacryl injection group. Conclusion: Therapeutic efficacy of Histoacryl injection was similar to the endoscopic band ligation in patients with esophageal varix bleeding in terms of hemostasis and rebleeding. Histoacryl is effective therapeutic option for esophageal variceal bleeding as well as gastric variceal bleeding. (Korean J Hepatol 1999;5:306－313)