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"Terlipressin"

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Liver fibrosis, cirrhosis, and portal hypertension

Hepatorenal syndrome: Current concepts and future perspectives
Chan-Young Jung, Jai Won Chang
Clin Mol Hepatol 2023;29(4):891-908.
Published online April 13, 2023
DOI: https://doi.org/10.3350/cmh.2023.0024
Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.

Citations

Citations to this article as recorded by  Crossref logo
  • Paracentesis exceeding three liters increases risks of acute kidney injury even in cirrhotic patients with albumin infused refractory ascites
    Pei-Shan Wu, Kuei-Chuan Lee, Chih-Yu Li, Yun-Cheng Hsieh, Teh-Ia Huo, Han-Chieh Lin, Ming-Chih Hou
    Journal of the Formosan Medical Association.2026; 125(3): 268.     CrossRef
  • Outcomes of Highly Urgent ABO-Incompatible Living Donor Liver Transplantation in National Databases
    Jongman Kim, Sang Jin Kim, Boram Park, Kyunga Kim, YoungRok Choi, Geun Hong, Jun Yong Park, Young Seok Han, Nam-Joon Yi, Seung Heui Hong, Soon-Young Kim, Jungbun Park, Youngwon Hwang, Dong-Hwan Jung
    Journal of Korean Medical Science.2026;[Epub]     CrossRef
  • Rising mortality due to coexisting liver cirrhosis and kidney failure in the United States (1999–2023): A nationwide retrospective analysis
    Muhammad Shaheer Bin Faheem, Syed Tawassul Hassan, Syeda Umbreen Munir, Muhammad Idrees Khan
    Medicine.2026; 105(9): e47662.     CrossRef
  • Neurofilament light chain proteins are a sensitive biomarker of neuronal damage in cirrhotic patients with hepatic encephalopathy
    Clelia Asero, Francesca Polito, Maria Stella Franzé, Antonio Battaglia, Claudia Ligresti, Teresa Maltese, Irene Cacciola, M’Hammed Aguennouz, Vincenzo Macaione
    Frontiers in Molecular Biosciences.2026;[Epub]     CrossRef
  • Trends and Demographics of Hepatorenal Syndrome-Related Mortality in the U.S., 1999–2024: A CDC WONDER Analysis
    Syed Faisal Ali, Julia Natche, Mahendrakumar Achlaram Chaudhari, Hassan Abbasi, Sammy Dawoud, Hany Dawoud, Amna Shoaib, Hersh Tilokani, Harleen Kaur Chela, Arsal Zafar
    Diseases.2026; 14(3): 106.     CrossRef
  • Fungal ribosomally synthesized and post-translationally modified peptides (F-RiPPs): Biosynthesis, genome mining, structural diversity, and translational potential as targeted anticancer ADC payloads
    S.T. Gopukumar, Madhumita Saha, Purbasha Das, Punniyamoorthy Sheela, M Komala, Jayaramareddy Harish, Karpakavalli Meenakshi Sundaram, Samer Shamshad, Uddalak Das
    Fitoterapia.2026; 192: 107283.     CrossRef
  • Association of visceral fat obesity with structural change in abdominal organs: fully automated three-dimensional volumetric computed tomography measurement using deep learning
    Haruka Kiyoyama, Masahiro Tanabe, Mayumi Higashi, Naohiko Kamamura, Yosuke Kawano, Kenichiro Ihara, Keiko Hideura, Katsuyoshi Ito
    Abdominal Radiology.2025; 50(9): 4395.     CrossRef
  • Understanding and Treating Hepatorenal Syndrome: Insights from Recent Research
    Yuli Song, Xiaochen Yang, Chengbo Yu
    Seminars in Liver Disease.2025; 45(03): 328.     CrossRef
  • Ascites complications risk factors of decompensated cirrhosis patients: logistic regression and prediction model
    Xiaolong Zheng, Wei Wei
    BMC Gastroenterology.2025;[Epub]     CrossRef
  • Emergency living donor liver transplantation
    Jongman Kim
    Annals of Liver Transplantation.2025; 5(1): 27.     CrossRef
  • Assessment of Albumin Therapy and Paracentesis Interval in Cirrhotic Patients With Recurrent Ascites: A Prospective Cohort Study
    Muhammad Abdullah Khan, Hafiz Muhammad Faizan Mughal, Shehwar Ahmed, M Khaliq, Abdul Ghafoor
    Cureus.2025;[Epub]     CrossRef
  • Acute Kidney Injury in Patients with Liver Cirrhosis: From Past to Present Definition and Diagnosis
    Andreea Lungu, Georgiana-Elena Sarbu, Alexandru Sebastian Cotlet, Ilie-Andreas Savin, Ioana-Roxana Damian, Simona Juncu, Cristina Muzica, Irina Girleanu, Ana-Maria Sîngeap, Carol Stanciu, Anca Trifan, Camelia Cojocariu
    Life.2025; 15(8): 1249.     CrossRef
  • Oral Branched-Chain Amino Acids as a Cost-Effective Option for Managing Hepatic Encephalopathy
    Hankil Lee, Sang Hoon Ahn, Beom Kyung Kim
    Yonsei Medical Journal.2025; 66(11): 713.     CrossRef
  • Life after hepatorenal syndrome: unraveling quality of life, psychological distress, and treatment preferences
    J. Müller-Kühnle, M. Schanz, J. Latus, D. Marschner, S. Schricker
    BMC Palliative Care.2025;[Epub]     CrossRef
  • The Kidney in the Shadow of Cirrhosis: A Critical Review of Renal Failure
    Livia-Mirela Popa, Paula Anderco, Oana Stoia, Cristian Ichim, Corina Porr
    Biomedicines.2025; 13(11): 2775.     CrossRef
  • Predicting risk factors for waiting mortality in adult emergent living donor liver transplantation based on Korean national data
    Sang Jin Kim, Jongman Kim, Kyunga Kim, Soon-Young Kim, Jung-Bun Park, Youngwon Hwang, Dong-Hwan Jung
    Annals of Liver Transplantation.2025; 5(2): 107.     CrossRef
  • VWF/ADAMTS13 Ratio as a Potential Predictive Biomarker for Acute Kidney Injury Onset in Cirrhosis
    Shohei Asada, Tadashi Namisaki, Kosuke Kaji, Hiroaki Takaya, Takahiro Kubo, Takemi Akahane, Hideto Kawaratani, Norihisa Nishimura, Soichi Takeda, Hiroyuki Masuda, Akihiko Shibamoto, Takashi Inoue, Satoshi Iwai, Fumimasa Tomooka, Yuki Tsuji, Yukihisa Fujin
    Digestive Diseases and Sciences.2024; 69(3): 851.     CrossRef
  • Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis
    Irina Efremova, Roman Maslennikov, Elena Poluektova, Oleg Medvedev, Anna Kudryavtseva, George Krasnov, Maria Fedorova, Filipp Romanikhin, Vyacheslav Bakhitov, Salekh Aliev, Natalia Sedova, Tatiana Kuropatkina, Anastasia Ivanova, Maria Zharkova, Ekaterina
    International Journal of Molecular Sciences.2024; 25(4): 1988.     CrossRef
  • Infection-Related Readmissions Are Rising among Patients with Hepatorenal Syndrome: A Nationwide Analysis
    Umer Farooq, Zahid I. Tarar, Ammad J. Chaudhary, Abdallah E. Alayli, Faisal Kamal, Chengdu Niu, Kamran Qureshi
    Livers.2024; 4(2): 268.     CrossRef
  • Management of hepatorenal syndrome and treatment-related adverse events
    Lorenzo Peluso, Marzia Savi, Giacomo Coppalini, Deliana Veliaj, Nicola Villari, Giovanni Albano, Stephen Petrou, Maria C. Pace, Marco Fiore
    Current Medical Research and Opinion.2024; 40(7): 1155.     CrossRef
  • Features of the course of hepatorenal syndrome in decompensated portal hypertension (case report)
    M.I. Tutchenko, D.V. Rudyk, M.S. Besedinskyi, S.L. Chub, Yu.V. Nerushchenko
    GASTROENTEROLOGY.2024; 58(2): 151.     CrossRef
  • Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats
    João Bruno Beretta Duailibe, Cassiana Macagnan Viau, Jenifer Saffi, Sabrina Alves Fernandes, Marilene Porawski
    World Journal of Nephrology.2024;[Epub]     CrossRef
  • Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function
    Xingyue Huang, Jas Bindra, Ishveen Chopra, John Niewoehner, George J. Wan
    Advances in Therapy.2023; 40(12): 5432.     CrossRef
  • 19,254 View
  • 1,540 Download
  • 21 Web of Science
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Case Reports

Liver fibrosis, cirrhosis, and portal hypertension

Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome
Hae Rim Kim, Young Sun Lee, Hyung Joon Yim, Hyun Joo Lee, Ja Young Ryu, Hyun Jung Lee, Eileen L. Yoon, Sun Jae Lee, Jong Jin Hyun, Sung Woo Jung, Ja Seol Koo, Rok Sun Choung, Sang Woo Lee, Jai Hyun Choi
Clin Mol Hepatol 2013;19(4):417-420.
Published online December 28, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.4.417

Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin.

Citations

Citations to this article as recorded by  Crossref logo
  • A Review of Terlipressin in Hepatorenal Syndrome: Targeting Endothelial Dysfunction and Subsequent Cardiovascular Adverse Events
    Adrienne M. Bielawski, William H. Frishman
    Cardiology in Review.2026; 34(3): 277.     CrossRef
  • The current applications and future directions of terlipressin
    Dorothy Liu, Adam Testro, Avik Majumdar, Marie Sinclair
    Hepatology Communications.2025;[Epub]     CrossRef
  • Comparison of 12- to 24-Hour Versus 72-Hour Intravenous Terlipressin in Patients With Acute Esophageal Variceal Bleeding: A Systematic Review and Meta-analysis
    Mohammad Al Hayek, Bisher Sawaf, Shahem Abbarh, Sudheer Dhoop, Abdallah Khashan, Ahmed Hassan, Alhasan Saleh Alzubi, Abdelrahman F. Abdelwahed, Abdussalam I. A. Alzein, Mohamedhen Vall Nounou, Yaseen Alastal, Muhammed Elhadi
    Journal of Pharmacy Technology.2025; 41(3): 124.     CrossRef
  • Terlipressin‐induced skin necrosis in cirrhotic patients—A case report and comprehensive literature review
    Ashraf I. Ahmed, Muhammad Zain Kaleem, Shahem Abbarh, Haider Hussein Barjas, Abdellatif Ismail, Mhd Kutaiba Albuni, Bisher Sawaf
    Clinical Case Reports.2024;[Epub]     CrossRef
  • Management of Established Small-for-size Syndrome in Post Living Donor Liver Transplantation: Medical, Radiological, and Surgical Interventions: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference
    Varvara A. Kirchner, Sadhana Shankar, David W. Victor, Tomohiro Tanaka, Nicolas Goldaracena, Roberto I. Troisi, Kim M. Olthoff, Jong Man Kim, Elizabeth A. Pomfret, Nigel Heaton, Wojtek G. Polak, Akash Shukla, Ravi Mohanka, Deniz Balci, Mark Ghobrial, Suba
    Transplantation.2023; 107(10): 2238.     CrossRef
  • Practice guidance for the use of terlipressin for liver cirrhosis–related complications
    Xingshun Qi, Zhaohui Bai, Qiang Zhu, Gang Cheng, Yu Chen, Xiaowei Dang, Huiguo Ding, Juqiang Han, Lei Han, Yingli He, Fanpu Ji, Hongxu Jin, Bimin Li, Hongyu Li, Yiling Li, Zhiwei Li, Bang Liu, Fuquan Liu, Lei Liu, Su Lin, Dapeng Ma, Fanping Meng, Ruizhao
    Therapeutic Advances in Gastroenterology.2022;[Epub]     CrossRef
  • Ischemic Bowel Syndrome in Patients with Spinal Cord Injury: A Nationwide Study
    Chih-Wei Tseng, Cheng-Li Lin, Yu-Tso Chen, Long-Bin Jeng, Michael G. Fehlings
    PLOS ONE.2017; 12(1): e0169070.     CrossRef
  • Double‐blind randomized controlled trial of the routine perioperative use of terlipressin in adult living donor liver transplantation
    Mettu Srinivas Reddy, Ilankumaran Kaliamoorthy, Akila Rajakumar, Selvakumar Malleeshwaran, Ellango Appuswamy, Sukanya Lakshmi, Joy Varghese, Mohamed Rela
    Liver Transplantation.2017; 23(8): 1007.     CrossRef
  • Ischemic Colitis Caused by Terlipressin during Treatment of Hepatorenal Syndrome
    Se Jin Park, Seung Hyun Lee, Ju Yeol Heo, Ki Wook Kim, Kyung-Ah Kim, June Sung Lee
    The Korean Journal of Medicine.2016; 90(5): 406.     CrossRef
  • Terlipressin

    Reactions Weekly.2014; 1523(1): 178.     CrossRef
  • 11,603 View
  • 118 Download
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Liver fibrosis, cirrhosis, and portal hypertension

A case of peripheral gangrene and osteomyelitis secondary to terlipressin therapy in advanced liver disease
Heon Ju Lee, Myung Jin Oh
Clin Mol Hepatol 2013;19(2):179-184.
Published online June 27, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.2.179

Variceal bleeding and hepatorenal syndrome (HRS) are serious and life-threatening complications of advanced liver disease. Terlipressin is widely used to manage both acute variceal bleeding and HRS due to its potency and long duration of action. The most severe (though rare) adverse event is ischemia. The present report describes the case of a patient with gangrene and osteomyelitis secondary to terlipressin therapy. A 71-year-old male with alcoholic liver cirrhosis (Child-Pugh B) and chronic hepatitis C was admitted due to a drowsy mental status. The patient had several experiences of orthopedic surgery. His creatinine level had gradually elevated to 4.02 mg/dL, and his urine output decreased to 500 mL/24 hr. The patient was diagnosed as having grade III hepatic encephalopathy (HE) and type II HRS. Terlipressin and albumin were administered intravenously to treat the HRS over 11 days. Although he recovered from the HE and HRS, the patient developed peripheral gangrene and osteomyelitis in both feet. His right toes were cured with the aid of rescue therapy, but his left three toes had to be amputated. Peripheral gangrene and osteomyelitis secondary to terlipressin therapy occur only rarely, and there is no specific rescue therapy for these conditions. Thus, attention should be paid to the possibility of ischemia of the skin and bone during or after terlipressin therapy.

Citations

Citations to this article as recorded by  Crossref logo
  • A Review of Terlipressin in Hepatorenal Syndrome: Targeting Endothelial Dysfunction and Subsequent Cardiovascular Adverse Events
    Adrienne M. Bielawski, William H. Frishman
    Cardiology in Review.2026; 34(3): 277.     CrossRef
  • The “dark” side of terlipressin: a case report of ischemic skin necrosis and review of literature
    Arpit Shastri, Sweta Rose, Nikhil Vojjala, Naveen Bhagat, Arka De
    Egyptian Liver Journal.2023;[Epub]     CrossRef
  • Practice guidance for the use of terlipressin for liver cirrhosis–related complications
    Xingshun Qi, Zhaohui Bai, Qiang Zhu, Gang Cheng, Yu Chen, Xiaowei Dang, Huiguo Ding, Juqiang Han, Lei Han, Yingli He, Fanpu Ji, Hongxu Jin, Bimin Li, Hongyu Li, Yiling Li, Zhiwei Li, Bang Liu, Fuquan Liu, Lei Liu, Su Lin, Dapeng Ma, Fanping Meng, Ruizhao
    Therapeutic Advances in Gastroenterology.2022;[Epub]     CrossRef
  • Symmetrical peripheral gangrene in critical illness
    Theodore E. Warkentin, Shuoyan Ning
    Transfusion and Apheresis Science.2021; 60(2): 103094.     CrossRef
  • Hepatorenal syndrome: pathophysiology and evidence-based management update
    Irtiza Hasan, Tasnuva Rashid, Razvan M Chirila, Peter Ghali, Hani M. Wadei
    Romanian Journal of Internal Medicine.2021; 59(3): 227.     CrossRef
  • Terlipressin-induced ischaemic skin necrosis
    Anand V Kulkarni, Pramod Kumar, Nagaraj P Rao, Nageshwar Reddy
    BMJ Case Reports.2020; 13(1): e233089.     CrossRef
  • Symmetrical Peripheral Gangrene: Mechanisms for Limb Loss in the ICU in Patients With Retained Pulses
    Theodore E. Warkentin
    Clinical Pulmonary Medicine.2018; 25(2): 61.     CrossRef
  • Cutaneous necrosis secondary to terlipressin therapy. A rare but serious side effect. Case report and literature review
    Enrique Iglesias Julián, Ester Badía Aranda, Belén Bernad Cabredo, Daniel Corrales Cruz, María José Romero Arauzo
    Revista Española de Enfermedades Digestivas.2017;[Epub]     CrossRef
  • Terlipressin-Induced Ischemic Skin Necrosis: A Rare Association
    Fatma Senel
    American Journal of Case Reports.2014; 15: 476.     CrossRef
  • Terlipressin

    Reactions Weekly.2014; 1488(1): 32.     CrossRef
  • 10,728 View
  • 87 Download
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Hepatology Elsewhere

Original Articles
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.
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.
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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