Clinical and Molecular Hepatology

"Ligation"

Review

Liver fibrosis, cirrhosis, and portal hypertension

Prevention and management of gastroesophageal varices: Yeon Seok Seo; Clin Mol Hepatol 2018;24(1):20-42.
Published online December 18, 2017; DOI: https://doi.org/10.3350/cmh.2017.0064

Abstract
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Bleeding from gastroesophageal varices is a serious complication in patients with liver cirrhosis and portal hypertension. Although there has been significance improvement in the prognosis of variceal bleeding with advancement in diagnostic and therapeutic modalities for its management, mortality rate still remains high. Therefore, appropriate prevention and rapid, effective management of bleeding from gastroesophageal varices is very important. Recently, various studies about management of gastoesophageal varices, including prevention of development and aggravation of varices, prevention of first variceal bleeding, management of acute variceal bleeding, and prevention of variceal rebleeding, have been published. The present article reviews published articles and practice guidelines to present the most optimal management of patients with gastroesophageal varices.

Citations

Citations to this article as recorded by

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Original Articles

Liver fibrosis, cirrhosis, and portal hypertension

Cyanoacrylate injection versus band ligation for bleeding from cardiac varices along the lesser curvature of the stomach: Sang Jung Park, Yong Kwon Kim, Yeon Seok Seo, Seung Woon Park, Han Ah Lee, Tae Hyung Kim, Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Jae Young Jang, Jong Eun Yeon, Kwan Soo Byun; Clin Mol Hepatol 2016;22(4):487-494.
Published online December 25, 2016; DOI: https://doi.org/10.3350/cmh.2016.0050

Abstract
PDF

Background/Aims
Practice guidelines recommend endoscopic band ligation (EBL) and endoscopic variceal obturation (EVO) for bleeding from esophageal varices and fundal varices, respectively. However, the optimal treatment for bleeding from cardiac varices along the lesser curvature of the stomach (GOV1) remains undefined. This retrospective study compared the efficacy between EBL and EVO for bleeding from GOV1.
Methods
Patients treated by EBL or EVO via cyanoacrylate injection for bleeding from GOV1 were enrolled. Patients diagnosed with hepatocellular carcinoma or treated with endoscopic injection sclerotherapy were excluded.
Results
The study included 91 patients treated for bleeding from GOV1. The mean age was 56.3±10.9 years (mean±SD), and 78 of them (85.7%) were men. Overall, 51 and 40 patients were treated with EBL and EVO, respectively. A trend for a higher hemostasis rate was noted in the EVO group (100%) than in the EBL group (82.6%, P=0.078). Varices rebled in 15 patients during follow-up. The rebleeding rate was significantly higher in the EBL group than in the EVO group (P=0.004). During follow-up, 13 patients died (11 in the EBL group and 2 in the EVO group); the survival rate was marginally significant between two groups (P=0.050). The rebleeding-free survival rate was significantly higher in the EVO group than in the EBL group (P=0.001).
Conclusions
Compared to EBL, EVO offered significantly lower rebleeding rates, significantly higher rebleeding-free survival rates, and a trend for higher hemostasis and survival rates. EVO appears to be the better therapeutic option for bleeding from GOV1.

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Endoscopic variceal ligation versus cyanoacrylate injection for acute variceal bleeding from the cardia to the lesser curvature
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Vascular disorders of liver

Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation: Ji Hye Jun, Jong Ho Choi, Si Hyun Bae, Seh Hoon Oh, Gi Jin Kim; Clin Mol Hepatol 2016;22(3):372-381.
Published online September 25, 2016; DOI: https://doi.org/10.3350/cmh.2016.0032

Abstract
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Background/Aims
Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL).
Methods
The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP.
Results
The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP.
Conclusions
CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

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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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Nonsurgical Secondary Prophylaxis of Esophageal Variceal Bleeding in Cirrhotic Patients
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Liver volume index predicts the risk of esophageal variceal hemorrhage in cirrhotic patients on propranolol prophylaxis
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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
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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
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Canadian Journal of Gastroenterology and Hepatology.2016; 2016: 1. CrossRef

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Serum hyaluronic acid Level: Correlation with quantitative measurement of hepatic fibrosis in a cirrhotic rat model: Moon Young Kim, M.D., Soon Koo Baik, M.D., Yoon Ok Jang, M.D., Ki Tae Suk, M.D., Jae Woo Kim, M.D., Hyun Soo Kim, M.D., Mi Yun Cho, M.D.1, Sun Joo Choi, M.D.2, Soon Ho Um, M.D.3, Kwang-Hyub Han, M.D.4; Korean J Hepatol 2008;14(2):159-167.
Published online June 20, 2008; DOI: https://doi.org/10.3350/kjhep.2008.14.2.159

Abstract
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Backgrounds/Aims
The serum level of hyaluronic acid (HA) has been suggested as a useful serologic marker for hepatic fibrosis. However, the relationship between serum HA levels and quantitative markers of fibrosis from liver tissue has not been reported. The aim of this study was to determine the correlation between serum HA level and quantitative measurement of hepatic fibrosis in a cirrhotic rat model. Methods: Cirrhosis was produced by common bile duct ligation (BDL) in adult Sprague-Dawley rats. The animals were classified into four groups: (1) G1, sham operated (n=5); (2) G2, BDL for 2 weeks (n=6); (3) G3, BDL for 3 weeks (n=6); and (4) G4, BDL for 4 weeks (n=6). Hepatic fibrosis was analyzed histomorphologically using the Batts and Ludwig scoring system. Serum HA level and hepatic hydroxyproline content were quantified. The gene expressions in the liver of procollagen, collagen, and transforming growth factor-β (TGF-β) were measured by reverse transcriptase-polymerase chain reaction. Results: In groups G1, G2, G3, and G4, the Batts and Ludwig scores (mean±SD) were 0, 1.3±0.5, 2.6±0.5, and 3.4±0.5, respectively (P<0.05), serum HA levels were 12.5±3.2, 30.0±4.3, 228.6±157.7, and 391.3±207.7 ng/mL (P<0.05), and the concentration of hydroxyproline was 12.4±2.8, 17.6±3.8, 17.9±2.4, and 33.4±3.4 μg/g liver tissue, and it was significantly higher in group G4 than in the other groups (P<0.05). The gene expressions of collagen, procollagen, and TGF-β1 in the liver were also significantly higher in group G4 compared with the other groups (P<0.05). Direct linear correlations were observed between serum HA level and hepatic hydroxyproline content, hepatic gene expressions of collagen, procollagen, TGF-β1, and histomorphological grade of hepatic fibrosis (P<0.001).
Conclusions
These results indicate that serum HA is a useful and noninvasive serologic marker for the evaluation of advanced hepatic fibrosis. (Korean J Hepatol 2008;14:159-167)

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Comparison of Endoscopic Variceal Ligation versus Combined Ligation and Sclerotherapy for Bleeding Esophageal Varices: Kyong Han Shin , June Sung Lee , Jung Hwan Yoon , Chul Joo Han , Hyo Suk Lee , Chung Yong Kim; Korean J Hepatol 1998;4(2):143-150.

Abstract
PDF

Background/Aims
' Combined esophageal variceal ligation and sclerotherapy has been hypothesized to be more effective for the control of bleeding esophageal varices than ligation alone. The present study was to compare the combined therapy with ligation alone in terms of variceal eradication, rebleeding, complication and survival rates in patients with bleeding esophageal varices. Methods Thirty-eight patients with bleeding esophageal varices were randomly assigned to receive ligation alone in 20 patients or the combined therapy in 18 patients. The clinical and endoscopic characteristics of patients in the ligation group were similar to those of patients in the combination group. In the combination group, 1-3 mL of ethanolamine was injected proximal to each ligated site. Treatments were repeated every 2- to 3-month until varices were eradicated. Results' No significant differences were found between the ligation and combination groups in variceal eradication rates (70% vs. 72%), numbers of endoscopic sessions required to achieve eradication (3.5+0.33 vs. 3.30.31), rebleeding rates (30% vs. 28%) or 2-yr cumulative survival rates (95% vs. 75%). There were significantly more complications in the combination group (25% vs. 89%, p=0.001). Conclusion' Ligation alone is recommended rather than the combined ligation and sclerotherapy because of its lower complication rates. (Korean J Hepatol 1998;4:143 - 150)

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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
PDF

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)