Intravenous Drip of Somatostatin Followed by Restricted Fluid Resuscitation to Treat Upper Gastrointestinal Bleeding in Patients with Liver Cirrhosis
Evidence-based complementary and alternative medicine : eCAM. 2021;2021:6548479
OBJECTIVE Liver cirrhosis is a common, often progressive, and usually fatal disorder. Upper gastrointestinal bleeding is a leading cause of death in patients with liver cirrhosis. The purpose of this study was to evaluate the effectiveness of somatostatin combined with restricted fluid resuscitation in the treatment of upper gastrointestinal bleeding in the patients with liver cirrhosis. METHODS From January 2018 to December 2020, 84 patients with liver cirrhosis complicated by upper gastrointestinal bleeding admitted to the Department of Gastroenterology of Ningbo Yinzhou No. 2 Hospital were selected as study participants. They were randomly assigned into the study group (n = 42) and control group (n = 42). All patients were given intravenous drip of somatostatin. The study group was supplemented with restricted fluid resuscitation therapy. The hemoglobin (Hb), platelet, fibrinogen, hematocrit, transfusion volume of red blood cells, hemostatic time, hemostatic rates in 0 h-24 h, 24 h-48 h, and >48 h, rebleeding rates, resuscitation rate, and incidence rates of complications were compared between the two groups 48 h after treatment. RESULTS It was found that the Hb, platelet, fibrinogen, and hematocrit were notably increased in the study group compared to the control group 48 h after treatment (P < 0.01). The proportion of patients with excellent response was notably higher in the study group than in the control group (P < 0.05). The overall response rate of the study group was 90.48%, which was significantly higher than 71.43% in the control group (P < 0.05). The study group had lower transfusion volume of red blood cells, shorter hemostatic time, and lower rebleeding rates than the control group (P < 0.01). The hemostatic rate of 0 h-24 h in the study group was remarkably higher than that in the control group (P < 0.05). The hemostatic rate of >48 h in the study group was lower than that in the control group (P < 0.05). The overall incidence rate of complications in the study group was 9.52%, which was significantly lower than 30.95% in the control group (P < 0.05). CONCLUSION These data suggest that intravenous drip of somatostatin followed by restricted fluid resuscitation leads to a better clinical efficacy in treating upper gastrointestinal bleeding in patients with liver cirrhosis considering higher resuscitation rate and hemostatic rate and reduced incidence of complications, which is conducive to the recovery of patients and worthy of further clinical promotion.
A prognostic score for patients with acute-on-chronic liver failure treated with plasma exchange-centered artificial liver support system
Scientific reports. 2021;11(1):1469
Artificial liver support system (ALSS) therapy is widely used in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop a predictive score to identify the subgroups who may benefit from plasma exchange (PE)-centered ALSS therapy. A total of 601 patients were retrospectively enrolled and randomly divided into a derivation cohort of 303 patients and a validation cohort of 298 patients for logistic regression analysis, respectively. Five baseline variables, including liver cirrhosis, total bilirubin, international normalized ratio of prothrombin time, infection and hepatic encephalopathy, were found independently associated with 3-month mortality. A predictive PALS model and the simplified PALS score were developed. The predicative value of PALS score (AUROC = 0.818) to 3-month prognosis was as capable as PALS model (AUROC = 0.839), R score (AUROC = 0.824) and Yue-Meng' score (AUROC = 0.810) (all p > 0.05), and superior to CART model (AUROC = 0.760) and MELD score (AUROC = 0.765) (all p < 0.05). The PALS score had significant linear correlation with 3-month mortality (R(2) = 0.970, p = 0.000). PALS score of 0-2 had both sensitivity and negative predictive value of > 90% for 3-month mortality, while PALS score of 6-9 had both specificity and positive predictive value of > 90%. Patients with PALS score of 3-5 who received 3-5 sessions of ALSS therapy had much lower 3-month mortality than those who received 1-2 sessions (32.8% vs. 59.2%, p < 0.05). The more severe patients with PALS score of 6-9 could still benefit from ≥ 6 sessions of ALSS therapy compared to ≤ 2 sessions (63.6% vs. 97.0%, p < 0.05). The PALS score could predict prognosis reliably and conveniently. It could identify the subgroups who could benefit from PE-centered ALSS therapy, and suggest the reasonable sessions.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032055. Registered 19th April 2020, http://www.chictr.org.cn/showproj.aspx?proj=52471 .
The pharmacodynamic effect of terlipressin versus high-dose octreotide in reducing hepatic venous pressure gradient: a randomized controlled trial
Annals of translational medicine. 2021;9(9):793
BACKGROUND Vasoactive drugs can reduce portal venous pressure and control variceal bleeding. However, few studies have explored the hemodynamic effects of terlipressin and high-dose octreotide in such patients. Our purpose was to evaluate the hemodynamic changes and safety of using terlipressin and high-dose octreotide in patients with decompensated liver cirrhosis. METHODS A multi-center randomized controlled trial was conducted. Cirrhotic patients with a history of variceal bleeding were included. Terlipressin or high-dose octreotide was administered during the procedure of measuring hepatic venous pressure gradient (HVPG). Hemodynamic parameters and symptoms were recorded. RESULTS A total of 88 patients were included. HVPG was significantly reduced at 10, 20, and 30 min after drug administration in the terlipressin group (16.3±6.4 vs. 14.7±5.9, 14.0±6.1, and 13.8±6.1, respectively, P<0.001) and the high-dose octreotide group (17.4±6.6 vs. 15.1±5.8, 15.3±6.2, and 16.1±6.0, respectively P<0.01). Decreased heart rate and increased mean arterial pressure were more often observed in the terlipressin group. The overall response rates were not significantly different between the groups (52.8% vs. 44.8%, P=0.524). The terlipressin group had significantly higher response rates at 30 min compared to the high-dose octreotide group in those with alcoholic liver cirrhosis [6/6 (100%) vs. 0/4 (0%), P=0.005]. The incidence of adverse drug events was rare and similar in the two groups. CONCLUSIONS Both terlipressin and high-dose octreotide were effective and safe for reducing HVPG. The pharmacodynamic effect of terlipressin persisted longer. The terlipressin group had higher response rates in those with alcoholic cirrhosis (trial number: NCT02119884).
Effects of dual plasma molecular adsorption system on liver function, electrolytes, inflammation, and immunity in patients with chronic severe hepatitis
Journal of clinical laboratory analysis. 2019;:e22926
BACKGROUND To investigate the effects of dual plasma molecular adsorption system (DPMAS) on the liver function, electrolytes, inflammation, and immunity in patients with chronic severe hepatitis (CSH). METHODS Total of 162 patients with CSH treated in our hospital from March 2016 to December 2018 were enrolled and equally randomly divided into control group (n = 81) and observation group (n = 81). The patients in control group were treated with plasma exchange, while those in observation group were additionally treated with DPMAS based on the treatment in control group. The liver function, electrolytes, inflammation, and immunity were evaluated and compared between the two groups. RESULTS After treatment, the liver function indexes in observation group were significantly favorable compared with those in control group, with the reduction in TBIL, DBIL, ALT, and rise of CHE levels (P < 0.05). The levels of K(+) , Na(+) , Cl(-) , and Ca(2+) in both groups were significantly improved after treatment (P < 0.05), although there were no significant differences between the two groups (P > 0.05). The levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in both groups declined after treatment compared with those before treatment, and those levels in observation group were higher than that in control group (P < 0.05). After treatment, the levels of cluster of differentiation 3(+) (CD3(+) ), CD4(+) , and CD4(+) /CD8(+) were higher in observation group than those in control group, with decreasing level of CD8(+) (P < 0.05). CONCLUSION Dual plasma molecular adsorption system can effectively improve the liver function, effectively correct the electrolyte disorders, reduce the inflammatory response, and adjust the immunity in patients with CSH.
Therapeutic plasma exchange: A prospective randomized trial to evaluate 2 strategies in patients with liver failure
Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis. 2018;57((2):):253-258
OBJECTIVE To compare two means of performing therapeutic plasma exchange (TPE) in patients with liver failure. METHOD This open-label monocentric randomized trial, conducted in a single prestigious general healthcare facility, recruited liver failure patients with an indication to receive artificial liver support therapy for TPE. All patients underwent TPE procedures and were administered in a random sequence: heparin-free or systemic heparinization with unfractionated heparin. The primary endpoint was completion of TPE sessions, and the secondary endpoints included the safety and efficacy. RESULTS In the period of the studying, there were 164 patients being recruited in and underwent total of 398 randomized TPEs: 168 with unfractionated heparin and 230 with heparin-free. In unfractionated heparin group, there were 3 cases (1.79%) being interrupted due to uncontrollable intraoperative pulmonary hemorrhages and gastrointestinal bleeding. In heparin-free group, 228 (99.13%) were completed successfully and 2 of them (0.87%) were switched from heparin-free to unfractionated heparin eventually. No significant differences were found between the two groups for either RRs or IRs (P>0.05). CONCLUSION Heparin-free regimen is feasible and safer than systemic heparinization with unfractionated heparin in the process of TPEs in patients with liver failure.
Avatrombopag Increases Platelet Count but Not Platelet Activation in Patients with Thrombocytopenia due to Liver Disease
Journal of Thrombosis and Haemostasis. 2018;16((12):):2515-2519.
BACKGROUND The thrombopoietin receptor agonist (TPO-RA) avatrombopag has recently been FDA-approved for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) scheduled for a procedure. The TPO receptor c-mpl is expressed on the platelet surface and TPO lowers the threshold for platelet activation. TPO-RAs may therefore also lead to platelet activation. OBJECTIVES To evaluate the effects of avatrombopag on platelet activation. PATIENTS/METHODS CLD patients with thrombocytopenia participated in a randomized, double-blind, placebo-controlled, parallel-group study. No patient received a platelet transfusion within 10 days of study blood draws. Platelet activation was evaluated by whole blood flow cytometry (which, unlike other methods, is accurate in thrombocytopenic samples). RESULTS Avatrombopag, but not placebo, increased platelet counts. As measured by platelet surface P-selectin and activated GPIIb-IIIa: 1) Circulating activated platelets were not increased in avatrombopag-treated patients compared with placebo-treated patients. 2) Platelet reactivity to low and high concentrations of ADP and thrombin receptor activating peptide was not increased in avatrombopag-treated patients compared with placebo-treated patients. CONCLUSIONS In this randomized, double-blind, placebo-controlled, parallel-group study of CLD patients with thrombocytopenia, avatrombopag increased platelet counts but did not increase platelet activation in vivo or platelet reactivity in vitro. This article is protected by copyright. All rights reserved.
Comparison of Endoscopic Variceal Ligation with Endoscopic Sclerotherapy for Secondary Prophylaxis of Variceal Hemorrhage: A Randomized Trial
Background Though endoscopic variceal ligation (EVL) is commonly being used and has overcome the disadvantages of sclerotherapy (ST), still sclerotherapy is used as a therapeutic procedure for bleeding esophageal varices in the present institute. Hence, the study was done to see the advantages of EVL over ST. Methods Patients with portal hypertension and bleeding esophageal varices underwent banding if found to have grade 3 or 4 varices. They were randomized to EVL group, where they were reviewed after two weeks for any residual varices for which repeat banding was done and endoscopic sclerotherapy (EST) group, where ST was done until the varices were obliterated or reduced to grade 1. The efficacy, complications, recurrent bleeding rate and recurrence of varices were compared. Results A total of 60 patients were included, 30 in each group. In EVL group, four sessions were needed to eradicate the varices in 73% of patients while it was five sessions in EST group (46% patients) (p-value = 0.0001). The mean number of sessions needed in EVL and EST group was 3.73 and 5.36, respectively. The average time taken for eradication of varices was 78.6 and 134.6 days in EVL and EST group, respectively (p-value = 0.004). Complications were higher in EST group (p-value < 0.05). Conclusion EVL alone was effective than ST in terms of the number of sessions needed for eradication of varices and total duration required to completely obliterate them. The complications were less in EVL group with no significant difference in recurrent bleeding rate and recurrence of varices between the groups.
Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies
Alimentary Pharmacology & Therapeutics. 2017;45((11):):1390-1402
BACKGROUND The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. AIM: To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. METHODS Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 mumol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1-2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. RESULTS The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of -53.0 mumol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. CONCLUSIONS Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT-0401, NCT00089570; REVERSE, NCT01143246).
Health-related quality of life in thrombocytopenic patients with chronic hepatitis C with or without cirrhosis in the ENABLE-1 and ENABLE-2 studies
Health & Quality of Life Outcomes. 2016;14((1)):49.
BACKGROUND Despite changes in the treatment paradigm towards non-interferon-based therapies, interferon-based treatments are still used in some geographical regions for treating patients with hepatitis C virus (HCV) infection. Use of eltrombopag with interferon-based treatment for patients with thrombocytopenia and HCV was assessed in two similarly designed phase 3 trials (Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects With Hepatitis C-Related Liver Disease [ENABLE-1 and ENABLE-2]). These trials also aimed to determine whether response to antiviral therapy (e.g., sustained virologic response [SVR]) is associated with changes in health-related quality of life (HRQoL). This pooled, post-hoc analysis aimed to (1) determine whether or not specific aspects of clinical response to treatment (i.e., achieving SVR) are associated with a significant change in HRQoL, and (2) to determine the magnitude and direction of the association between important changes in HRQoL, clinical response to interferon-based therapy (e.g., SVR) and treatment (eltrombopag or placebo), and patient and disease attributes. METHODS The Short-Form 36 Health Survey version 2 and Chronic Liver Disease Questionnaire-Hepatitis C Virus version were administered at various time points during the studies. Results from both trials were pooled for the analyses. Logistic regression analysis was used to assess the influence of 5 clinical factors (SVR, early virologic response [EVR], genotype [2/3 vs. non-2/3], treatment [eltrombopag or placebo], and cumulative interferon dose), plus other factors including ethnicity, model of end-stage liver disease score, and platelets as predictors of meaningful changes in HRQoL. RESULTS Between antiviral therapy baseline and the end of the 24-week post-treatment follow-up, declines in HRQoL were smaller in eltrombopag-treated patients than in placebo-treated patients, but the differences were not statistically significant. Mean changes among patients achieving SVR and EVR were small in comparison to thresholds of minimally important changes. Logistic models did not confirm the strength of the 5 clinical factors as predictors of meaningful changes in HRQoL during antiviral therapy, with the exception of the interaction between SVR and EVR (P=0.0009). Asian ethnicity had a consistent effect on HRQoL, with East Asian patients being more likely to experience deterioration in HRQoL compared with white and/or other non-East Asian patients. CONCLUSIONS While on active antiviral therapy, declines in HRQoL were not statistically different for eltrombopag-treated patients versus placebo-treated patients, suggesting that eltrombopag neither worsened HRQoL nor mitigated the effects of antiviral therapy on HRQoL.
Pre exchange albumin administration in neonates with hyperbilirubinemia: a randomized controlled trial
Indian Pediatrics. 2015;52((9)):763-7.
OBJECTIVE To evaluate the efficacy of pre-exchange transfusion albumin priming in neonates with non-hemolytic hyperbilirubinemia. DESIGN Single center, randomized controlled trial. SETTING Level III Neonatal unit. PARTICIPANTS Fifty healthy term and late preterm neonates with non-hemolytic hyperbilirubinemia requiring exchange transfusion. INTERVENTIONS 5 mL/kg of either 20% human albumin (n=23) or 0.9% saline (n=27) infusion one hour prior to exchange transfusion. MAIN OUTCOME MEASURE Post-exchange transfusion phototherapy duration. RESULTS The post-exchange transfusion phototherapy duration was not different between albumin and saline groups [Median (IQR): 29 (24-48) h vs. 33 (24-43) h; P=0.76]. The total amount of bilirubin removed during exchange transfusion was also similar [Median (IQR): 34 (28-46) mg vs. 33 (27-38) mg; P=0.46]. Serial changes in total serum bilirubin following exchange transfusion and need for repeat exchange transfusion were comparable between the groups. CONCLUSIONS In healthy late preterm and term neonates with non-hemolytic hyperbilirubinemia, priming with 1 g/kg of 20% albumin prior to exchange transfusion is not superior to equi-volume 0.9% saline in reducing post- exchange transfusion phototherapy duration or amount of bilirubin mass removed.