RESUMEN
BACKGROUND AND AIMS: Observational studies suggest a beneficial effect of continuous terlipressin infusion (CTI) on ascites and sarcopenia in decompensated cirrhosis with portal hypertension. APPROACH AND RESULTS: This single-center, prospective, cross-over study randomized 30 patients with cirrhosis, ascites, and sarcopenia to commence on 12 weeks of home CTI or 12 weeks of observation prior to cross-over. The co-primary outcomes were change in handgrip strength and paracentesis volume. Secondary outcomes included quality of life, sarcopenia measures, renal function, safety, and hospitalization. The median age of participants was 62 years (IQR: 57-64), the median Model for End-Stage Liver Disease-Sodium was 16 (12.3-20.8), and 22 (73%) were male. Handgrip strength increased by a mean adjusted difference (MAD) of 3.09 kg (95% CI: 1.11-5.08 kg) between CTI and observation ( p =0.006); an 11.8% increase from baseline. The total volume of ascites drained decreased by a MAD of 11.39L (2.99-19.85, p =0.01), with 1.75 fewer episodes of paracentesis (0.925-2.59, p <0.001) on CTI. Serum creatinine decreased, urinary sodium excretion increased, and quality of life was significantly higher on CTI (all p <0.001), with an increase in Chronic Liver Disease Questionnaire score of 0.41 points (0.23-0.59). There were 7 minor line-related complications but no cardiac events or pulmonary edema. CONCLUSIONS: This novel study demonstrates a significant increase in handgrip strength, reduction in paracentesis volume, and improved quality of life in patients with decompensated cirrhosis treated with continuous terlipressin infusion. These findings provide a strong rationale for the use of ambulatory CTI in appropriately selected patients with cirrhosis.
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Ascitis , Estudios Cruzados , Fuerza de la Mano , Cirrosis Hepática , Terlipresina , Humanos , Masculino , Persona de Mediana Edad , Ascitis/tratamiento farmacológico , Ascitis/etiología , Terlipresina/administración & dosificación , Estudios Prospectivos , Femenino , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Infusiones Intravenosas , Vasoconstrictores/administración & dosificación , Sarcopenia/prevención & control , Sarcopenia/tratamiento farmacológico , Sarcopenia/etiología , Calidad de Vida , Hipertensión Portal/tratamiento farmacológico , AncianoRESUMEN
Hepatorenal syndrome (HRS) is associated with a dismal prognosis in patients with cirrhosis, and therapeutic options are limited. Biomarkers to identify patients with poor response to therapy are urgently needed. This study aimed to evaluate the predictive value of serum levels of uromodulin (sUMOD) in patients with cirrhosis and HRS treated with terlipressin and albumin (T/A). In total, 156 patients [81 patients with HRS treated with T/A, 42 patients with cirrhosis without kidney injury, and 33 patients with cirrhosis with prerenal acute kidney injury (AKI)] were included. sUMOD levels were analyzed by ELISA. Patients with HRS were prospectively followed for the composite endpoint of hemodialysis-/liver transplantation-free survival (HD/LTx-free survival). Of the 81 patients with HRS, 40 had HRS type 1 and 41 type 2. In the cohort of patients with HRS treated with T/A, median sUMOD level was 100 ng/mL (IQR 64; 144). sUMOD differed significantly between patients with HRS compared with patients without AKI (P = 0.001) but not between patients with HRS and prerenal AKI (P = 0.9). In multivariable analyses, sUMOD levels in the lowest quartile were independently associated with a lower rate of complete response to T/A (OR 0.042, P = 0.008) and a higher risk for reaching the composite endpoint of HD/LTX-free survival (HR 2.706, P = 0.013) in patients with HRS type 2 treated with T/A. In contrast, sUMOD was not significantly associated with these outcomes in patients with HRS type 1. sUMOD may be a valuable biomarker for identifying patients with HRS type 2 treated with T/A to predict response and prognosis.NEW & NOTEWORTHY Biomarkers identifying patients with hepatorenal syndrome (HRS) and poor response to therapy are urgently needed. In this study, lower serum uromodulin (sUMOD) levels were associated with poorer response to therapy with terlipressin and albumin and consequently with poorer prognosis in patients with HRS type 2. In patients with HRS type 1, there was no association between sUMOD and poorer prognosis.
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Lesión Renal Aguda , Síndrome Hepatorrenal , Humanos , Síndrome Hepatorrenal/terapia , Síndrome Hepatorrenal/tratamiento farmacológico , Terlipresina/uso terapéutico , Uromodulina , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Pronóstico , Biomarcadores , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , AlbúminasRESUMEN
Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a severe complication of cirrhosis that carries a poor prognosis. The recent Food and Drug Administration approval of terlipressin has substantial implications for managing HRS-AKI and liver allocation in the United States. Terlipressin has been available in Europe for over a decade, and several countries have adapted policy changes such as Model for End-Stage Liver Disease (MELD) score "lock" for HRS-AKI. In this article, we outline the European experience with terlipressin use and explore the question of whether terlipressin treatment for HRS-AKI should qualify for the MELD score "lock" in the United States in those who respond to therapy. Arguments for the MELD lock include protecting waitlist priority for terlipressin responders or partial responders who may miss offers due to MELD reduction in the terlipressin treatment window. Arguments against MELD lock include the fact that terlipressin may produce a durable response and improve overall survival and that equitable access to terlipressin is not guaranteed due to cost and availability. We subsequently discuss the proposed next steps for studying terlipressin implementation in the United States. A successful approach will require the involvement of all major stakeholders and the mobilization of our transplant community to spearhead research in this area.
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Lesión Renal Aguda , Síndrome Hepatorrenal , Trasplante de Hígado , Índice de Severidad de la Enfermedad , Terlipresina , Vasoconstrictores , Listas de Espera , Humanos , Terlipresina/uso terapéutico , Trasplante de Hígado/normas , Trasplante de Hígado/estadística & datos numéricos , Trasplante de Hígado/efectos adversos , Estados Unidos , Síndrome Hepatorrenal/etiología , Síndrome Hepatorrenal/diagnóstico , Listas de Espera/mortalidad , Vasoconstrictores/uso terapéutico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Europa (Continente) , Selección de Paciente , Pronóstico , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: The definition and diagnostic criteria of hepatorenal syndrome-acute kidney injury (HRS-AKI) has undergone recent changes. A major vasoconstrictor, terlipressin, has recently been approved as pharmacotherapy for HRS-AKI in the United States. The purpose of this review is to familiarize the readers with these new diagnostic criteria of HRS-AKI, and how best to use terlipressin. RECENT FINDINGS: Terlipressin is effective either as bolus dosing or continuous infusion and can achieve reversal of HRS-AKI in approximately 40% of patients. Continuous infusion allows lower daily dose with equal efficacy and less side effects but not an approved mode of administration in the United States. Response to terlipressin in the randomized controlled trials was defined as repeat reduction of serum creatinine to less than 1.5âmg/dl. Newer studies will likely require response to treatment to be defined as a repeat serum creatinine to be less than 0.3âmg/dl from baseline. Terlipressin use is associated with ischemic side effects and potential for respiratory failure development. SUMMARY: Careful patient selection and close monitoring are necessary for its use. Response to terlipressin with HRS-AKI reversal is associated with improved outcomes with better survival and less requirement for renal replacement therapy.
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Lesión Renal Aguda , Síndrome Hepatorrenal , Humanos , Terlipresina/uso terapéutico , Lipresina/uso terapéutico , Lipresina/efectos adversos , Síndrome Hepatorrenal/tratamiento farmacológico , Creatinina/uso terapéutico , Resultado del Tratamiento , Vasoconstrictores/uso terapéutico , Vasoconstrictores/efectos adversos , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamenteRESUMEN
BACKGROUND AND AIMS: Terlipressin infusion is effective in hepatorenal syndrome (HRS-AKI). However, its efficacy for HRS-AKI resolution in acute-on-chronic liver failure (ACLF) patients has been suboptimal. Progression of AKI is rapid in ACLF. We investigated whether early initiation of terlipressin(eTerli) can improve response rates. METHODS: Consecutive ACLF patients with stage II/III AKI despite albumin resuscitation (40 g) were randomized to receive terlipressin at 2 mg/24 h plus albumin at 12 h (ET, n = 35) or at 48 h as standard therapy (ST, n = 35). (June 22, 2020 to June 10, 2022). The primary end-point was AKI reversal by day7. RESULTS: Baseline parameters including AKI stage and ACLF-AARC scores in two arms were comparable. Full AKI response at day 7 was higher in ET [24/35 (68.6%)] than ST arm [11/35 (31.4%; P 0.03]. Day3 AKI response was also higher in ET arm [11/35 (31.4%) vs. 4/35 (11.4%), P 0.04]. Using ST compared to ET [HR 4.3; P 0.026] and day 3 serum creatinine > 1.6 mg/dl [HR 9.1; AUROC-0.866; P < 0.001] predicted HRS-AKI non-response at day 7. ET patients showed greater improvement in ACLF grade, mean arterial pressure, and urine output at day 3, and required lower albumin within 7 days than ET arm (149.1 ± 41.8 g vs. 177.5 ± 40.3 g, P 0.006) and had lower 28-day mortality: 40% vs. 65.7%, P 0.031]. Early use of terlipressin than ST [HR 2.079; P 0.038], baseline HE [HR 2.929; P 0.018], and AKI persistence at day 3 [HR 1.369; P 0.011] predicted 28-day mortality. Fifteen (21.4%) patients had treatment related adverse effects, none was life threatening. CONCLUSION: In ACLF patients, early initiation of terlipressin for AKI persisting after 12 h of volume expansion with albumin helps in reduced short-term mortality and early AKI reversal with regression of ACLF stage. These results indicate need for change in current practice for terlipressin usage in HRS-AKI.
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Lesión Renal Aguda , Insuficiencia Hepática Crónica Agudizada , Terlipresina , Vasoconstrictores , Humanos , Terlipresina/administración & dosificación , Masculino , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Femenino , Persona de Mediana Edad , Vasoconstrictores/administración & dosificación , Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Insuficiencia Hepática Crónica Agudizada/complicaciones , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adulto , Resultado del Tratamiento , Anciano , Factores de Tiempo , Tiempo de TratamientoRESUMEN
INTRODUCTION AND OBJECTIVES: Hepatorenal syndrome (HRS) is a serious complication of cirrhosis treated with various medications. We aim to evaluate terlipressin and albumin's effectiveness and safety compared to albumin and noradrenaline in adult hepatorenal disease patients. MATERIALS AND METHODS: Clinical trials from four databases were included. Cochrane's approach for calculating bias risk was utilized. We rated the quality evaluation by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included the following outcomes: serum creatinine (mg/dl), urine output (ml/24 h), mean arterial pressure (mmHg), reversal rate of HRS, mortality rate, blood plasma renin activity (ng/ml/h), plasma aldosterone concentration (pg/ml), urine sodium (mEq/l), and creatinine clearance (ml/min). RESULTS: Our analysis of nine clinical studies revealed that the noradrenaline group was associated with higher creatinine clearance (MD = 4.22 [0.40, 8.05]), (P = 0.03). There were no significant differences in serum creatinine levels (MD = 0.03 [-0.07, 0.13]), urinary sodium (MD = -1.02 [-5.15, 3.11]), urine output (MD = 32.75 [-93.94, 159.44]), mean arterial pressure (MD = 1.40 [-1.17, 3.96]), plasma renin activity (MD = 1.35 [-0.17, 2.87]), plasma aldosterone concentration (MD = 55.35 [-24.59, 135.29]), reversal rate of HRS (RR = 1.15 [0.96, 1.37]), or mortality rate (RR = 0.87 [0.74, 1.01]) between the two groups (p-values > 0.05). CONCLUSIONS: Noradrenaline is a safe alternative medical therapy for HRS.
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Albúminas , Síndrome Hepatorrenal , Norepinefrina , Terlipresina , Vasoconstrictores , Humanos , Terlipresina/uso terapéutico , Síndrome Hepatorrenal/tratamiento farmacológico , Norepinefrina/uso terapéutico , Norepinefrina/orina , Norepinefrina/sangre , Albúminas/uso terapéutico , Resultado del Tratamiento , Vasoconstrictores/uso terapéutico , Vasoconstrictores/efectos adversos , Adulto , Creatinina/sangre , Lipresina/análogos & derivados , Lipresina/uso terapéutico , Lipresina/efectos adversosAsunto(s)
Lesión Renal Aguda , Síndrome Hepatorrenal , Lipresina , Terlipresina , Vasoconstrictores , Humanos , Terlipresina/uso terapéutico , Síndrome Hepatorrenal/tratamiento farmacológico , Lesión Renal Aguda/diagnóstico , Lipresina/análogos & derivados , Lipresina/uso terapéutico , Lipresina/efectos adversos , Vasoconstrictores/uso terapéutico , Vasoconstrictores/efectos adversosAsunto(s)
Lesión Renal Aguda , Síndrome Hepatorrenal , Terlipresina , Vasoconstrictores , Humanos , Terlipresina/uso terapéutico , Síndrome Hepatorrenal/tratamiento farmacológico , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/inducido químicamente , Vasoconstrictores/uso terapéutico , Vasoconstrictores/efectos adversos , Lipresina/análogos & derivados , Lipresina/efectos adversos , Lipresina/uso terapéuticoAsunto(s)
Terlipresina , Humanos , Terlipresina/administración & dosificación , Gabapentina/administración & dosificación , Gabapentina/uso terapéutico , Vasoconstrictores/administración & dosificación , Vasoconstrictores/efectos adversos , Lipresina/análogos & derivados , Lipresina/administración & dosificación , Lipresina/efectos adversos , MasculinoAsunto(s)
Síndrome Hepatorrenal , Trasplante de Hígado , Humanos , Terlipresina/uso terapéutico , Trasplante de Hígado/efectos adversos , Vasoconstrictores/uso terapéutico , Lipresina/uso terapéutico , Albúminas/uso terapéutico , Resultado del Tratamiento , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
INTRODUCTION: Liver disease causes 2 million deaths annually, accounting for 4% of all deaths worldwide. Liver surgery is one of the effective therapeutic options. Bleeding is a major complication during liver surgery. Perioperative bleeding and allogeneic blood transfusion may deteriorate the prognosis. Terlipressin (TP), a synthetic analogue of the antidiuretic hormone, may reduceblood loss during abdominal surgery. Several clinical centres have attempted to use TP during liver surgery, but the evidence for its effectiveness in reducing blood loss and the need for allogeneic blood transfusion, as well as its safety during the perioperative period, remains unclear. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of TP in reducing blood loss and allogeneic blood transfusion needs during liver surgery. METHODS AND ANALYSIS: We will search PubMed, EMBASE, the Cochrane Library and Web of Science for studies on perioperative use of TP during liver surgery from inception to July 2023. We will limit the language to English, and two reviewers will independently screen and select articles. The primary study outcomes are estimated blood loss and the need for allogeneic blood transfusion. Secondary outcomes include operating time, intensive care unit stay, length of stay, intraoperative urine output, acute kidney injury rate, postoperative complications, hepatic and renal function during follow-up, and TP-related adverse effects. We will include studies that met the following criteria: (1) randomised controlled trials (RCTs), cohort studies or case-control studies; (2) the publication time was till July 2023; (3) adult patients (≥18 years old) undergoing elective liver surgery; (4) comparison of TP with other treatments and (5) the study includes at least one outcome. We will exclude animal studies, case reports, case series, non-original articles, reviews, paediatric articles, non-controlled trials, unpublished articles, non-English articles and other studies that are duplicates. We will use Review Manager V.5.3 software for meta-analysis and perform stratification analysis for the study quality of RCTs based on the Jadad score. For cohort or case-control studies, the study quality will be analysed based on Newcastle-Ottawa Scale scores. Grading of Recommendations, Assessment, Development and Evaluation will be used to assess confidence in the cumulative evidence. For primary outcomes, we will conduct subgroup analyses based on meta-regression. We will also perform leave-one-out sensitivity analyses to evaluate the effect of each individual study on the combined results by removing the individual studies one by one for outcomes with significant heterogeneity. The protocol follows the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines. ETHICS AND DISSEMINATION: This study is a secondary analysis of existing data; therefore, it does not require ethical approval. We will disseminate the results through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023450333.
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Pérdida de Sangre Quirúrgica , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto , Terlipresina , Vasoconstrictores , Humanos , Terlipresina/uso terapéutico , Terlipresina/administración & dosificación , Pérdida de Sangre Quirúrgica/prevención & control , Vasoconstrictores/administración & dosificación , Vasoconstrictores/uso terapéutico , Proyectos de Investigación , Hepatopatías/cirugía , Transfusión Sanguínea/estadística & datos numéricos , Hígado/cirugíaRESUMEN
Hepatorenal syndrome (HRS) is a feared complication in patients with advanced cirrhosis and is associated with significant morbidity and mortality. While recognized as a distinct physiologic condition for well over one hundred years, a lack of objective diagnostic tests has made the diagnosis one of exclusion. Since 1979, multiple sets of diagnostic criteria have been proposed. Though varying in detail, the principal intent of these criteria is to identify patients with severe, functional acute kidney injury that is unresponsive to volume resuscitation and exclude those with structural injury. However, accurate differential diagnosis remains challenging. Recently, multiple urinary biomarkers of kidney injury, including neutrophil gelatinase-associated lipocalin, have been studied as a means of objectively phenotyping etiologies of acute kidney injury in patients with cirrhosis. Along with markers reflecting tubular functional integrity, including the fractional excretion of sodium, injury markers will likely be incorporated into future diagnostic criteria. Making an accurate diagnosis is critical, as therapeutic options exist for HRS but must be given in a timely manner and only to those patients likely to benefit. Terlipressin, an analog of vasopressin, is the first line of therapy for HRS in much of the world and has recently been approved for use in the United States. Significant questions remain regarding the optimal dosing strategy, metrics for titration, and the potential role of point-of-care ultrasound to help guide concurrent albumin administration.
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Biomarcadores , Síndrome Hepatorrenal , Terlipresina , Humanos , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/terapia , Síndrome Hepatorrenal/etiología , Biomarcadores/orina , Terlipresina/uso terapéutico , Lipresina/análogos & derivados , Lipresina/uso terapéutico , Vasoconstrictores/uso terapéutico , Diagnóstico Diferencial , Lipocalina 2/orina , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapiaRESUMEN
BACKGROUND: Hepatorenal syndrome (HRS), a multiorgan condition of acute kidney injury, is seen in advanced liver disease. This study aims to evaluate the current treatment for HRS. METHODS: The authors searched PubMed, Scopus and Google Scholar literature. After quality assessment, 31 studies were included in this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology and the population, intervention, comparison and outcome scheme were used. We included human-controlled trials that evaluate the current treatment for HRS. Two authors independently screened articles for inclusion, extracted data and assessed the quality of included studies. RESULTS: This study investigated the studies conducted on the effects of different treatments on follow-up of HRS patients. We gathered 440 articles, so 31 articles remained in our study. Of which 24 articles were conducted on terlipressin versus placebo or other treatments (midodrine/octreotide, norepinephrine, etc) that showed the higher rate of HRS reversal was detected for terlipressin in 17 studies (10 of them were significant), 2 studies achieved an insignificant lower rate of the model for end-stage liver disease score for terlipressin, 15 studies showed a decreased mortality rate in the terlipressin group (4 of them were significant). CONCLUSION: This review showed that terlipressin has a significantly higher reversal rate of HRS than the other treatments. Even the results showed that terlipressin is more efficient than midodrine/octreotide and norepinephrine as a previous medication, in reverse HRS, increasing patient survival.
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Enfermedad Hepática en Estado Terminal , Síndrome Hepatorrenal , Midodrina , Humanos , Terlipresina/uso terapéutico , Vasoconstrictores/uso terapéutico , Midodrina/uso terapéutico , Síndrome Hepatorrenal/tratamiento farmacológico , Octreótido/uso terapéutico , Índice de Severidad de la Enfermedad , Norepinefrina/uso terapéuticoRESUMEN
Cirrhosis is a liver disease that leads to increased intrahepatic resistance, portal hypertension (PH), and splanchnic hyperemia resulting in ascites, variceal bleeding, and hepatorenal syndrome. Terlipressin, a prodrug that converts to a short half-life vasopressin receptor 1 A (V1a) full agonist [8-Lys]-Vasopressin (LVP), is an intravenous treatment for PH complications, but hyponatremia and ischemic side effects require close monitoring. We developed PHIN-214 which converts into PHIN-156, a more biologically stable V1a partial agonist. PHIN-214 enables once-daily subcutaneous administration without causing ischemia or tissue necrosis and has a 10-fold higher therapeutic index than terlipressin in healthy rats. As V1a partial agonists, PHIN-214 and PHIN-156 exhibited maximum activities of 28 % and 42 % of Arginine vasopressin (AVP), respectively. The potency of PHIN-156 and LVP relative to AVP is comparable for V1a (5.20 and 1.65 nM, respectively) and V1b (102 and 115 nM, respectively) receptors. However, the EC50 of PHIN-156 to the V2 receptor was 26-fold higher than that of LVP, indicating reduced potential for dilutional hyponatremia via V2 agonism compared to terlipressin/LVP. No significant off-target binding to 87 toxicologically relevant receptors were observed when evaluated in vitro at 10 µM concentration. In bile duct ligated rats with PH, subcutaneous PHIN-214 reduced portal pressure by 13.4 % ± 3.4 in 4 h. These collective findings suggest that PHIN-214 could be a novel pharmacological treatment for patients with PH, potentially administered outside of hospital settings, providing a safe and convenient alternative for managing PH and its complications.
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Várices Esofágicas y Gástricas , Hiponatremia , Humanos , Ratas , Animales , Receptores de Vasopresinas/metabolismo , Terlipresina , Hemorragia Gastrointestinal , Vasopresinas , Arginina Vasopresina/farmacologíaRESUMEN
BACKGROUND: In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear. AIMS: We aimed to compare efficacy of 1-day versus 3-day terlipressin therapy in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks. METHODS: In this open-label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1-day or 3-day terlipressin therapy. RESULTS: A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day (n = 75) or 3 days (n = 75) of terlipressin therapy. One patient from 1-day arm was excluded. Modified intention-to-treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4-9.0) versus 4 (5.3%; 95% CI: 2.0-10.0), risk difference (RD) p = 0.726 and 5-day mortality rates: 1 (1.4%; 95% CI: 0-7.3) versus 1 (1.3%; 95% CI: 0.2-7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0-20.0) versus 10 (13.3%; 95% CI: 7.0-20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0-10.0) versus 4 (5.3%; 95% CI: 2.0-10.0), RD p = 0.704 were also similar. Patients in the 1-day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026. CONCLUSIONS: Our results suggest that 1 day of terlipressin therapy is associated with similar 5-day and 42-day rebleeding rates, 42-day mortality and an overall superior safety profile compared with 3-day of terlipressin therapy. These findings require to be validated in double-blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).
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Várices Esofágicas y Gástricas , Cirrosis Hepática , Terlipresina , Humanos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/inducido químicamente , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Proyectos Piloto , Terlipresina/administración & dosificación , Terlipresina/efectos adversos , Várices/complicaciones , Vasoconstrictores/administración & dosificación , Vasoconstrictores/efectos adversosRESUMEN
We present the case of a woman in her 60s with Child-Pugh C cirrhosis who developed pericardial tamponade during an admission for a haemothorax secondary to a mechanical fall. The patient developed haemodynamic compromise with a rapid decline in renal function. During an open subxiphoid drain tube insertion, a pre-existing peritoneopericardial communication was noted, with ascites in the peritoneal cavity on view. The serum ascites albumin gradient was 14 g/L. Maximal medical therapy was commenced including diuresis and albumin, with adjunctive terlipressin infusion which restored her baseline renal function and resolved the effusion. We believe this is the first case report of using open drainage, maximal medical therapy and terlipressin to successfully treat hepatic hydropericardium and its subsequent renal compromise.
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Ascitis , Derrame Pericárdico , Femenino , Humanos , Terlipresina/uso terapéutico , Ascitis/tratamiento farmacológico , Ascitis/etiología , Riñón , Cirrosis Hepática/complicaciones , Derrame Pericárdico/complicaciones , Edema/complicaciones , Albúminas , Drenaje/efectos adversos , Lipresina/uso terapéuticoRESUMEN
BACKGROUND: Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation. AIM: The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation. METHODS: Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes. RESULTS: A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82-4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%-CI 2.96-30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22-23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001). CONCLUSIONS: Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.
Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Humanos , Terlipresina/efectos adversos , Farmacorresistencia Bacteriana Múltiple/genética , Antibacterianos/efectos adversos , Factores de Riesgo , Cirrosis Hepática/tratamiento farmacológico , BacteriasRESUMEN
The treatment of choice for hepatorenal syndrome-acute kidney injury (HRS-AKI) is vasoconstrictor therapy in combination with albumin, preferably norepinephrine or terlipressin as recommended by recent guidelines. In the absence of larger head-to-head trials comparing the efficacy of terlipressin and norepinephrine, meta-analysis of smaller studies can provide insights needed to understand the comparative effects of these medications. Additionally, recent changes in the HRS diagnosis and treatment guidelines underscore the need for newer analyses comparing terlipressin and norepinephrine. In this systematic review, we aimed to assess reversal of hepatorenal syndrome (HRS) and 1-month mortality in subjects receiving terlipressin or norepinephrine for the management of HRS-AKI. We searched literature databases, including PubMed, Cochrane, Clinicaltrials.gov, International Clinical Trials Registry Platform, Embase, and ResearchGate, for randomized controlled trials (RCTs) published from January 2007 to June 2023 on June 26, 2023. Only trials comparing norepinephrine and albumin with terlipressin and albumin for the treatment of HRS-AKI in adults were included, and trials without HRS reversal as an endpoint or nonresponders were excluded. Pairwise meta-analyses with the random effects model were conducted to estimate odds ratios (ORs) for HRS reversal and 1-month mortality as primary outcomes. Additional outcomes assessed, included HRS recurrence, predictors of response, and incidence of adverse events (AEs). We used the Cochrane risk of bias assessment tool for quality assessment. We included 7 RCTs with a total of 376 subjects with HRS-AKI or HRS type 1. This meta-analysis showed numerically higher rates of HRS reversal (OR 1.33, 95% confidence interval [CI] [0.80-2.22]; P = 0.22) and short-term survival (OR 1.50, 95% CI [0.64-3.53]; P = 0.26) with terlipressin, though these results did not reach statistical significance. Terlipressin was associated with AEs such as abdominal pain and diarrhea, whereas norepinephrine was associated with cardiovascular AEs such as chest pain and ischemia. Most of the AEs were reversible with a reduction in dose or discontinuation of therapy across both arms. Of the terlipressin-treated subjects, 5.3% discontinued therapy due to serious AEs compared to 2.7% of the norepinephrine-treated subjects. Limitations of this analysis included small sample size and study differences in HRS-AKI diagnostic criteria. As more studies using the new HRS-AKI criteria comparing terlipressin and norepinephrine are completed, a clearer understanding of the comparability of these 2 therapies will emerge.
Asunto(s)
Lesión Renal Aguda , Síndrome Hepatorrenal , Adulto , Humanos , Terlipresina/uso terapéutico , Norepinefrina/efectos adversos , Síndrome Hepatorrenal/tratamiento farmacológico , Lipresina/efectos adversos , Resultado del Tratamiento , Vasoconstrictores/efectos adversos , Lesión Renal Aguda/inducido químicamente , Albúminas/efectos adversosRESUMEN
Variceal bleeding is a major complication and the leading cause of death in patients with cirrhosis and portal hypertension. This study aims to compare the efficacy and safety of terlipressin vs octreotide as an adjuvant to endoscopic management of patients with esophageal variceal bleeding in a real-time scenario. We reviewed the medical records of patients with esophageal variceal bleeding from January 2005 to December 2020 at our tertiary care Aga Khan University Hospital. Mortality was assessed after 6 weeks. A total of 842 patients with variceal bleed were evaluated. 624 patients (74.1%) and 218 patients (25.9%) received Terlipressin and Octreotide respectively. On multiple regression analysis, cardiac events during hospital stay (OR: 11.22), presence of Porto-systemic encephalopathy (OR: 3.79), and elevated bilirubin levels at the time of presentation were found to be independent risk factors for increased six weeks mortality. Moreover, cardiac events during hospital stay (OR: 3.26), Porto-systemic encephalopathy at presentation (OR: 3.06), and octreotide administration (OR: 1.80) were identified as independent risk factors for increased length of hospital stay. Terlipressin and Octreotide have similar outcomes in terms of control of bleeding, hospital stay, mortality, and side effects when used as adjuvant therapy for the management of variceal bleeding.