Vasoactive drugs form the mainstay of therapy for two of the most important complications of liver disease: hepatorenal syndrome (HRS) and acute variceal bleed (AVB). With cumulative evidence supporting the use in cirrhosis, terlipressin has been recommended for the management of HRS and AVB. However, owing to the safety concerns, terlipressin was not approved by food and drug administration (FDA) until now. In this review, we discuss the pharmacology and the major practice‐changing studies on the safety and efficacy of terlipressin in patients with cirrhosis particularly focusing on existing indications like AVB and HRS and reviewing new data on the expanding indications in liver disease. The references for this review were identified from PUBMED with MeSH terms such as “terlipressin,” “hepatorenal syndrome,” “varices, esophagal and gastric,” “ascites” and “cirrhosis.” Terlipressin, a synthetic analogue of vasopressin, was introduced in 1975 to overcome the adverse effects of vasopressin. Terlipressin is an effective drug for HRS reversal in patients with liver cirrhosis and acute‐on‐chronic liver failure. There is documented mortality benefit with terlipressin therapy in HRS and AVB. Adverse effects are common with terlipressin and need to be monitored strictly. There is some evidence to support the use of this drug in refractory ascites, hepatic hydrothorax, paracentesis‐induced circulatory dysfunction and perioperatively during liver transplantation. However, terlipressin is not yet recommended for such indications. In conclusion, terlipressin has stood the test of time with expanding indications and clear prerequisites for clinical use. Our review warrants a fresh perspective on the efficacy and safety of terlipressin.

Annually, 10% of cirrhotic patients with ascites develop refractory ascites for which large-volume paracentesis (LVP) is a frequently used therapeutic procedure. LVP, although a safe method, is associated with circulatory dysfunction in a significant percentage of patients, which is termed paracentesis-induced circulatory dysfunction (PICD). PICD results in faster reaccumulation of ascites, hyponatremia, renal impairment, and shorter survival. PICD is diagnosed through laboratory results, with increases of >50% of baseline plasma renin activity to a value $4 ng/mL/h on the fifth to sixth day after paracentesis. In this review, we discuss the pathophysiology and prevention of PICD.

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.

Background: Acute-on-chronic liver failure (ACLF) is a syndrome of acute portal hypertension with high shortterm mortality. ACLF patients have low mean arterial pressure (MAP), systemic vascular resistance, and high cardiac output. This, in turn, leads to an increased incidence of ascites, acute kidney injury, and hyponatremia. We evaluated the role of the early addition of midodrine, which has not been analyzed to date. Methods: ACLF patients who were started on midodrine (Gr. A) in addition to standard of care (SOC) for ascites control were included and compared with those who received only SOC (Gr. B). The aim was to assess the hemodynamics, ascites control, diuretic-related complications, and mortality at 1 month. Results: Forty-five ACLF patients (Gr. A-21; Gr. B-24) were included in the pilot study. At inclusion, the baseline characteristics were similar among the groups. The dose of midodrine was 22.5 (7.5-22.5) mg/day for 22.29 ± 8.75 days in Gr. A. Midodrine significantly improved the MAP and urinary sodium excretion. Only 33.34% of patients required paracentesis in Gr. A compared with 62.5% in Gr. B (p = 0.05). Gr. A patients tolerated a higher dose of diuretics than Gr. B. Diuretic-related complications developed in 54.2% of patients in Gr. B compared with only 23.8% in Gr. A (p = 0.03). Fourteen percent in Gr. A developed side effects to midodrine and required dose modification. Mortality at day 30 was similar in both groups. Conclusion: Addition of midodrine improves the hemodynamics, tolerability of diuretics, and ascites control in ACLF patients. ( J CLIN EXP HEPATOL xxxx;xxx:xxx)