Clinical and Molecular Hepatology

"Propranolol"

Original Articles

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.

Citations

Citations to this article as recorded by

Analysis of risk factors for hospital-acquired pneumonia in schizophrenia
Yu-hang Chen, Cong-ying Ren, Yu Liao
Frontiers in Psychiatry.2024;[Epub] CrossRef
Combined Pharmacological and Endoscopic Treatment for Worsening Gastroesophageal Varices in Patients with Cirrhosis
Veronica Pepe, Paolo Angeli, Marco Di Pascoli
Clinical and Experimental Gastroenterology.2022; Volume 15: 59. CrossRef
Nonsurgical Secondary Prophylaxis of Esophageal Variceal Bleeding in Cirrhotic Patients
Liwei Jing, Qiumeng Zhang, Ziwei Chang, Hui Liu, Xuan Shi, Xingyu Li, Jing Wang, Yanbo Mo, Xiujing Zhang, Lizhuan Ma, Zhiting Li, Chao Zhang
Journal of Clinical Gastroenterology.2021; 55(2): 159. CrossRef
Influencing Factors of Hospital-Acquired Pneumonia Infection in the Middle-Aged and Elderly Patients With Schizophrenia
Mi Yang, Qiwen Li, Chunzhi Wang, Li Li, Min Xu, Fei Yan, Wei Chen, Ying Wan
Frontiers in Psychiatry.2021;[Epub] CrossRef
Long-term outcome of endoscopic variceal band ligation of esophageal varices in patients with chronic liver disease
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

11,681 View
95 Download
10 Web of Science
Crossref

The Comparision of Propranolol Monotherapy and Propranolol , Isosorbide - 5 - mononitrate and Metoclopramide Triple Therapy after Endoscopic Sclerotherapy in Patients with Esophageal Variceal Bleeding: Jin Bae Kim , Oh Young Lee , Dong Soo Han , Joo Hyun Sohn , Ho Soon Choi , Byung Chul Yoon , Joon Soo Hahm , Min Ho Lee , Kyung Nam Park , Choon Suhk Kee; Korean J Hepatol 1997;3(2):114-122.

2,764 View
16 Download

Changes of Propranolol Pharmacokinetic Parameters According to Hepatic Fibrotic Severity in CCl₄-Treated Rats: Mun Su Kang, M.D., Chang Ok Yoon, M.D., Jai Won Byun, M.D., Oh Young Lee, M.D. Byung Chul Yoon, M.D., Joon Soo Hahm, M.D., Ju Seop Kang, M.D.*, Min Ho Lee, M.D.; Korean J Hepatol 2001;7(2):181-188.

Abstract
PDF

Background/Aims
This study was designed to determine the effect of hepatic fibrotic severity on pharmacokinetics of propranolol in CCl₄-treated rats.Methods:1 mL/kg of 10% CCl₄ in olive oil was injected intramuscularly to rats twice weekly for 4, 6, 8 and 10 weeks, respectively(n=6). Control(n=6) was a sham-injected equal dose of olive oil for 10 weeks. After intravenous bolus injection of 2 mg/kg propranolol to rats, the serum propranolol concentrations were analyzed for 4 hours at various time points by a HPLC-fluorimetric system, and pharmacokinetic parameters such as C₀, MRT, AUC, Vdss, t_1/2(β) and CLp were determined. Then, a small amount of hepatic tissue was obtained and subjected to determination of the hepatic 4-hydroxyproline content, which confirmed the hepatic fibrotic severity. Results:The serum concentrations of propranolol at 0.5, 1, 2 and 4 hours were significantly increased in CCl₄-treated rats(p<0.01). In proportion to the duration of CCl₄ treatment, C₀ and AUC were significantly increased, and Vdss and CLp were significantly decreased(p<0.001). But MRT and t_1/2(β) were not significantly changed. The hepatic 4-hydroxyproline content was gradually increased in CCl₄-treated rats(p<0.001).Conclusion:Gradual changes in pharmacokinetic parameters of propranolol were seen to be dependent on the hepatic fibrotic severity. We suggest that gradual dosage modification, according to their hepatic fibrotic severity, is necessary for many drugs administered to patients with chronic liver disease.(Korean J Hepatol 2001;7:181-188)

3,099 View
17 Download

Relationship of Propranolol Pharmacokinetic Parameters with Portosystemic Shunt in CCl₄ - induced cirrhotic Rats: Dong Hee Koh, M.D., Geun Tae Park, M.D., Jung Mi Kim, M.D., Yeong Seop Yun, M.D., Sung Hee Lee, M.D., Dong Uk Kim, M.D., Jin Bae Kim, M.D., Yun Yung Choi, M.D.*, Ju Seop Kang, M.D.**, Ho Soon Choi, M.D., Joon Soo Hahm, M.D., Min Ho Lee, M.D.; Korean J Hepatol 2002;8(3):277-287.

Abstract
PDF

Background
This study was designed to determine the relationship of propranolol pharmacokinetic parameters with portosystemic shunt in CCl₄-induced cirrhotic rats. Methods: Cirrhotic rats(n=6) were induced by intramuscular injection of CCl₄ in olive oil(two time per weeks) for 12 weeks. Controls (n=6) were injected intramuscularly with the same dose of olive oil for 12 weeks. We evaluated the amount of portosystemic shunt by thallium-201 per rectal scintigraphy. After intravenous bolus injection of propranolol (2mg/kg) to rats, the serum propranolol concentrations were analyzed by a HPLC-fluorimetric detector system. Pharmacokinetic parameters such as C₀, AUC, t_1/2(β), and CLp were determined in each group. Then, a small amount of heptic tissue was obtained and subjected to determination of the hepatic collagen content by quantitating 4-hydroxyproline and were inspected by microscope after hematoxylin and eosin stain. Results: In liver biopsy, liver fibrosis progressed in CCl₄-induced cirrhotic rats. The serum concentrations of propranolol were significantly (p<0.01) elevated in CCl₄-induced cirrhotic rats. Mean amount of 4-hydroxyproline, mean H/L ratio, and mean AUC in CCl₄-induced cirrhotic rats was significantly (p<0.01) higher than that in control rats. There was a relationship between AUC, H/L ratio, and amount of 4-hydroxyproline. Conclusion: H/L ratio may help in the selection of drug dosage (especially blood flow dependent drug) in pre-clinical studies for chronic liver disease during the drug development process. (Korean J Hepatol 2002;8:277-287)