Endothelin-1/Nitric Oxide Ratio as a Predictive Factor of Response to Therapy With Terlipressin and Albumin in Patients With Type-1 Hepatorenal Syndrome

Abdel‐Razik, Ahmed; Mousa, Nasser; Abdelsalam, Mostafa; Abdel‐Wahab, Ahmed; Tawfik, Mona K.; Tawfik, Ahmed; Hasan, Ahmad S.; Elhelaly, Rania; El‐Wakeel, Niveen; Eldars, Waleed

doi:10.3389/fphar.2020.00009

Cited by 9 publications

(5 citation statements)

References 52 publications

(58 reference statements)

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“…Randomized trials with low-dose terlipressin or alternate day terlipressin therapy may be utilized to reduce the adverse effects of terlipressin in patients with ACLF. Endothelin-1/Nitric oxide ratio aid in predicting response to terlipressin therapy 28 . Serum endothelin levels, nitric oxide, lactate dehydrogenase levels may be used to monitor and predict the ischemic adverse events of terlipressin.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study

Kulkarni

Ravikumar

Tevethia

et al. 2022

Sci Rep

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Terlipressin with albumin, the recommended treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), is associated with adverse events. Furthermore, the course of AKI in patients with acute-on-chronic liver failure (ACLF) is unknown. We aimed to analyze the safety and efficacy of terlipressin infusion and AKI course in patients with ACLF. We prospectively enrolled consecutive adult patients with ACLF with HRS-AKI (satisfying EASL criteria) treated with terlipressin infusion between 14 October 2019 and 24 July 2020. The objectives were to assess the incidence of adverse events, response to terlipressin, course of HRS-AKI and predictors of mortality. A total of 116 patients were included. Twenty-one percent of patients developed adverse effects. Only 1/3rd of patients who developed adverse events were alive at day 90. Sixty-five percent of the patients responded to terlipressin. Nearly 22% developed recurrence of HRS, and 5.2% progressed to HRS-chronic kidney disease. TFS was 70.4% at day 30 and 57.8% at day 90. On multivariate stepwise Cox regression analysis terlipressin non-response (hazard ratio [HR], 3.49 [1.85–6.57]; P < 0.001) and MELD NA score (HR,1.12 [1.06–1.18]; P < 0.001) predicted mortality at day-90. Patients with ACLF who develop terlipressin related adverse events have dismal prognoses. Terlipressin non-response predicts mortality in patients with ACLF and HRS-AKI.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study

Kulkarni

Ravikumar

Tevethia

et al. 2022

Sci Rep

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“…In previous works [ 17 , 22 ], we demonstrated that the pyruvate tolerance test is a good tool to assess the liberation of HGO in the fasting state. G6Pase can control hyperglycemia because it determines the production of glucose released from gluconeogenesis and glycogenolysis [ 23 ]; therefore, inhibition of this rate-limiting enzyme is a target to treat hyperglycemia in T2D.…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemic Effect of Calea urticifolia (Mill.) DC.

Andrade‐Cetto

Espinoza-Hernández

Mata-Torres

2021

Evidence-Based Complementary and Alternative Medicine

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The onset of type 2 diabetes (T2D) is a consequence of the progressive loss of adequate β-cell insulin secretion, which frequently occurs under a background of insulin resistance. Currently, nearly 13 million Mexicans are living with diabetes. Moreover, due to poor socioeconomic conditions and the cultural idiosyncrasies of the Mexican population, the use of medicinal plants to treat T2D is a common practice in Mexico. In the Mexican state of Hidalgo, we found the traditional use of Calea urticifolia (CU) to treat this disease. To treat T2D, people drink an infusion made from the aerial part of the plant throughout the day. With the aim of investigating whether the infusion at a traditional dose produces a hypoglycemic effect in either the fasting or postprandial state, we measured the effect of the infusion in a hyperglycemic animal model (rats administered streptozotocin (STZ) and nicotinamide (NZ)) by conducting a glucose tolerance test and constructing a blood-glucose curve. We then analyzed whether the observed effect was related to the inhibition of glucose absorption in the gut or the inhibition of hepatic glucose output (HGO) in vivo and in vitro. Furthermore, we confirmed our findings by identifying the potential targets of the infusion via a network pharmacology analysis. Through high-performance liquid chromatography (HPLC) and thin layer chromatography (TLC), we detected a number of compounds in the extract and identified two of them. The plant extract produced a highly significant hypoglycemic effect under fasting conditions and a weak hypoglycemic effect following glucose or sucrose challenge. Although the plant extract blocked only 20% of the alpha-glucosidase enzyme activity in vitro, in the pyruvate tolerance test (which measures the liberation of hepatic glucose), it significantly reduced glucose levels. Furthermore, in vitro, the extract diminished the activity of the glucose-6-phosphatase complex by 90%. In addition, by conducting TLC, we detected the presence of chlorogenic acid and rutin, which have been reported to block HGO. The results presented here provide evidence of the hypoglycemic effect of the traditionally used C. urticifolia extract and demonstrate that this effect is associated with both a reduction in glucose synthesis via gluconeogenesis due to the phytochemical composition of the extract and a slight blockage of glucose absorption in the gut.

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“…Randomized trials with low dose terlipressin or alternate day terlipressin therapy may be utilized to reduce the adverse effects of terlipressin in patients with ACLF. Endothelin-1/Nitric oxide ratio aid in predicting response to terlipressin therapy [30]. Serum endothelin levels, nitric oxide, lactate dehydrogenase levels may be used to monitor and predict the ischemic adverse events of terlipressin.…”

Section: Discussionmentioning

confidence: 99%

Safety And Efficacy of Terlipressin In Acute-On-Chronic Liver Failure With Acute Kidney Injury – A Prospective Cohort Study

Kulkarni

T.R

Tevethia

et al. 2021

Preprint

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Background: Terlipressin with albumin, the recommended treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), is associated with adverse events. Furthermore, the course of AKI in patients with acute-on-chronic liver failure (ACLF) is unknown. We aimed to analyze the safety and efficacy of terlipressin infusion and AKI course in patients with ACLF.Methods: We prospectively enrolled consecutive adult patients with ACLF with HRS-AKI (satisfying either EASL or APASL criteria) treated with terlipressin infusion between 14 October 2019 and 24 July 2020. The objectives were to assess the incidence of adverse events, response to terlipressin, and differential treatment response in EASL and APASL subgroups. Results: Of the 116 patients, 51 satisfied EASL criteria, and 65 satisfied APASL criteria. Twenty-one percent of patients developed adverse effects. Only 1/3rd of patients who developed adverse events were alive at day 90. Sixty-five percent of the patients responded to terlipressin. Nearly 22% developed recurrence of HRS, and 5.2% progressed to HRS-chronic kidney disease. Response to terlipressin was higher in EASL (78.43%) than APASL subgroup (53.84%;P=0.006). Terlipressin non-response predicted mortality in EASL (aHR,6.35[1.15-35.13];P=0.03) and APASL subgroups (aHR,3.07[1.47-6.4];P=0.003).Conclusion: ACLF patients who develop terlipressin adverse events have dismal prognoses. Terlipressin non-response predicts mortality in patients with ACLF and HRS-AKI.

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Endothelin-1/Nitric Oxide Ratio as a Predictive Factor of Response to Therapy With Terlipressin and Albumin in Patients With Type-1 Hepatorenal Syndrome

Cited by 9 publications

References 52 publications

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study

Hypoglycemic Effect of Calea urticifolia (Mill.) DC.

Safety And Efficacy of Terlipressin In Acute-On-Chronic Liver Failure With Acute Kidney Injury – A Prospective Cohort Study

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