scholarly journals A Phase II Dose Escalation Study of Intraarterial (Hepatic) Adult Human Bone Marrow Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells (Stempeucel®) in Patients with Alcoholic Liver Cirrhosis

2021 ◽  
pp. 1-19
Author(s):  
Pawan Kumar Gupta ◽  
Pawan Kumar Gupta ◽  
Anoop Chullikana ◽  
Raviraja NS ◽  
Uday kumar K ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Adverse Events ◽  
Short Form ◽  
Control Group ◽  
Alcoholic Liver Cirrhosis ◽  
Short Form 36 ◽  
Respective Control ◽  
End Stage

Background: Alcoholic liver cirrhosis is an end-stage alcoholic liver disease with a poor prognosis. The definitive treatment of alcoholic liver cirrhosis is orthotopic liver transplantation, which is expensive, requires long-term immunosuppression and is limited by the supply of organs. Being an unmet medical need, cell therapy is under investigation for alcoholic liver cirrhosis. Aims: This study was designed primarily for assessing the safety and feasibility of administering stempeucel® through the hepatic artery in alcoholic liver cirrhosis and secondarily to assess possible efficacy and dose-response. Methods: Sixty patients with alcoholic cirrhosis (18-65 years/Child-Pugh class B or C/Model for End-Stage Liver Disease score of minimum 10) were planned to be included in 6 groups: 2.5 million cells/kg Body Weight (2.5M Cell) and respective control (2.5M Control); 5 million cells/kg Body Weight (5M Cell) and respective control (5M Control); 7.5 million cells/kg Body Weight (5M Cell) and respective control (7.5M Control) with 10 patients in each group. Cell groups received stempeucel® administered via hepatic artery by catheterization through the femoral artery (Seldinger technique) and Standard Protocol of Care. The control group received Standard Protocol of Care. Patients were followed up at 1 week, 1 month, 3 months and 6 months. Efficacy evaluations included liver function test, Model for End-Stage Liver Disease score, Child-Pugh score, Short Form-36 questionnaire, liver stiffness using Fibroscan (Transient Elastography), and liver volume using Computerized Tomography scan. Results: Stempeucel® injection was well tolerated. Common treatment-emergent adverse events were gastrointestinal disorders, general disorders and administration site conditions and infections and infestations. Most of the treatment-emergent adverse events were unrelated / remotely related to stempeucel®. Thirty serious adverse events occurred in 10 patients (3 in 2.5M Cell, 5 in 5M Cell and one each in control groups). Three patients died due to SAEs: Two in 2.5M and one in 5M Cell group, none were related to stempeucel®. Statistically significant improvement was seen in 2.5M group compared to the control group in Short Form-36 score: bodily pain, mental component summary, vitality and social functioning. Conclusion: Stempeucel® was safe, well-tolerated and subjective improvement in Short Form-36 (bodily pain, mental component summary, vitality and social functioning and mental health) score was seen in the 2.5M cell group.

scholarly journals A Phase Ii Dose Escalation Study of Intraarterial (Hepatic) Adult Human Bone Marrow Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells (Stempeucel®) in Patients with Alcoholic Liver Cirrhosis

2021 ◽  
Author(s):  
Pawan Kumar Gupta ◽  
Anoop Chullikana ◽  
Raviraja N Seetharam ◽  
Udaykumar Kolkundar ◽  
Shivashankar P ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Adverse Events ◽  
Short Form ◽  
Cell Group ◽  
Control Group ◽  
Alcoholic Liver Cirrhosis ◽  
Short Form 36 ◽  
End Stage Liver Disease ◽  
End Stage

Abstract Background: Alcoholic liver cirrhosis is an end stage alcoholic liver disease with poor prognosis. The definitive treatment of alcoholic liver cirrhosis is orthotopic liver transplantation, which is expensive, requires long term immunosuppression and is limited by supply of organs. Being an unmet medical need, cell therapy is under investigation for alcoholic liver cirrhosis.Aims: This study was designed primarily for assessing the safety and feasibility of administering stempeucel® through the hepatic artery in alcoholic liver cirrhosis and secondarily to assess possible efficacy and dose-response.Methods: Forty patients with alcoholic cirrhosis (18-65 years/Child Pugh class B or C/Model for End-Stage Liver Disease score of minimum 10) were included in 4 groups: 2.5 million cells/kg Body Weight (2.5M Cell) and respective control (2.5M Control); 5 million cells/kg Body Weight (5M Cell) and respective control (5M Control) with 10 patients in each group. Cell groups received stempeucel® administered via hepatic artery by catheterization through femoral artery (Seldinger technique) and Standard Protocol of Care. Control group received Standard Protocol of Care. Patients were followed up at 1 week, 1 month, 3 months and 6 months. Safety evaluations included clinical examination, Electrocardiogram and laboratory investigations. Efficacy evaluations included liver function test, Model for End-Stage Liver Disease score, Child Pugh score, Short Form-36 questionnaire, liver stiffness using Fibroscan (Transient Elastography), and liver volume using Computerized Tomography scan. Results: stempeucel® injection was well tolerated. Common treatment emergent adverse events were in Gastrointestinal disorders, General disorders and administration site conditions and Infections and infestations. Most of the treatment emergent adverse events were unrelated / remotely related to stempeucel®. Thirty serious adverse events occurred in 10 patients (3 in 2.5M Cell, 5 in 5M Cell and one each in control groups). Three patients died due to SAEs: Two in 2.5M and one in 5M Cell group, none were related to stempeucel®. There was no significant difference in efficacy evaluations at 6 months versus baseline compared to control at both the dose levels of stempeucel®. Statistically significant improvement was seen in 2.5M group compared to control group in Short Form-36 score: bodily pain, mental component summary, vitality and social functioning. Conclusions: stempeucel® was safe, well tolerated and subjective improvement in few component scores of Short Form-36 was seen 2.5M cell group.Trial registrationClinicaltrials.gov: NCT01591200Clinical Trial Registry – India: CTRI/2009/091/000432

scholarly journals Assessment of serum level cholinesterase as a biomarker of liver cirrhosis in Egyptian cirrhotic patients

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Mona A. Amin ◽  
Marwa E. El-Shahat ◽  
Nouman El-Garem ◽  
Ahmed Soliman ◽  
Eman Obaia
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Negative Correlation ◽  
Meld Score ◽  
Serum Cholinesterase ◽  
Control Group ◽  
Strong Negative Correlation ◽  
Compensated Cirrhosis ◽  
Cirrhotic Patients ◽  
End Stage

Serum cholinesterase levels are closely correlated with the severity of liver disease. The aim of the paper was to assess the value of serum cholinesterase in evaluating liver reserve function in cirrhotic patients. 90 patients with liver cirrhosis and thirty healthy control group were included. Liver cirrhosis patients were classified according to child score into three equal groups: Child A liver cirrhosis, Child B liver cirrhosis and Child C liver cirrhosis. Patients were subjected to clinical evaluation, laboratory analysis, abdominal U/S. Measuring serum cholinesterase, and Calculation of both Child and model of end stage liver disease (MELD) scores. The level of serum cholinesterase was higher in control group than the three groups of liver cirrhosis with median (IQR) 17,410 (12,111-21,774), 7528 (5200-9856), 6021 (4500-7542), 3828.5 (1541-6060), respectively P<0.001). And the level of serum cholinesterase was higher in Child A more than Child B and Child C and the level of serum cholinesterase was higher in Child B more than Child C with very strong negative correlation between serum Cholinesterase level and Child score (r=-0.9, P<0.001). Also strong negative correlation between serum Cholinesterase level and MELD score (r=- 0.85, P=0.001), and positive correlation with prothrombin concentration (r=0.554, P=0.009), and serum albumin levels (r=0.582, P=0.0002). Serum cholinesterase is a good biomarker of cirrhosis. Since it distinguishes decompensated from compensated cirrhosis well, low levels in cirrhosis may serve as a useful prognostic marker of advanced liver disease.

scholarly journals Doppler ultrasound in liver cirrhosis: correlation of hepatic artery and portal vein measurements with model for end-stage liver disease score in Egypt

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Ahmed Abdelrahman Mohamed Baz ◽  
Rana Magdy Mohamed ◽  
Khaled Helmy El-kaffas
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Portal Vein ◽  
Hepatic Artery ◽  
Meld Score ◽  
Hepatic Decompensation ◽  
End Stage Liver Disease ◽  
Cirrhotic Patients ◽  
Us Findings ◽  
End Stage

Abstract Background Liver cirrhosis is a multi-etiological entity that alters the hepatic functions and vascularity by varying grades. Hereby, a cross-sectional study enrolling 100 cirrhotic patients (51 males and 49 females), who were diagnosed clinically and assessed by model for end-stage liver disease (MELD) score, then correlated to the hepatic Doppler parameters and ultrasound (US) findings of hepatic decompensation like ascites and splenomegaly. Results By Doppler and US, splenomegaly was evident in 49% of patients, while ascites was present in 44% of them. Increased hepatic artery velocity (HAV) was found in70% of cases, while 59% showed reduced portal vein velocity (PVV). There was a statistically significant correlation between HAV and MELD score (ρ = 0.000), but no significant correlation with either hepatic artery resistivity index (HARI) (ρ = 0.675) or PVV (ρ =0.266). Moreover, HAV had been correlated to splenomegaly (ρ = 0.000), whereas HARI (ρ = 0.137) and PVV (ρ = 0.241) did not significantly correlate. Also, ascites had correlated significantly to MELD score and HAV (ρ = 0.000), but neither HARI (ρ = 0.607) nor PVV (ρ = 0.143) was significantly correlated. Our results showed that HAV > 145 cm/s could confidently predict a high MELD score with 62.50% and 97.62 % sensitivity and specificity. Conclusion Doppler parameters of hepatic vessels (specifically HAV) in addition to the US findings of hepatic decompensation proved to be a non-invasive and cost-effective imaging tool for severity assessment in cirrhotic patients (scored by MELD); they could be used as additional prognostic parameters for improving the available treatment options and outcomes.

scholarly journals Right Heart Remodeling in Patients with End-Stage Alcoholic Liver Cirrhosis: Speckle Tracking Point of View

2019 ◽  
Vol 8 (9) ◽  
pp. 1285 ◽  
Author(s):  
Kun Zhang ◽  
Alexander Braun ◽  
Francisca von Koeckritz ◽  
Rosa B. Schmuck ◽  
Eva M. Teegen ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Systolic Function ◽  
Global Longitudinal Strain ◽  
Meld Score ◽  
Right Atrial ◽  
Alcoholic Liver Cirrhosis ◽  
Basal Diameter ◽  
Cirrhotic Patients ◽  
End Stage ◽  
Longitudinal Strains

Background: Data regarding cardiac remodeling in patients with alcoholic liver cirrhosis are scarce. We sought to investigate right atrial (RA) and right ventricular (RV) structure, function, and mechanics in patients with alcoholic liver cirrhosis. Methods: This retrospective cross-sectional investigation included 67 end-stage cirrhotic patients, who were referred for evaluation for liver transplantation and 36 healthy controls. All participants underwent echocardiographic examination including strain analysis, which was performed offline. Results: RV basal diameter and RV thickness were significantly higher in patients with cirrhosis. Conventional parameters of the RV systolic function were similar between the observed groups. Global, endocardial, and epicardial RV longitudinal strains were significantly lower in patients with cirrhosis. Active RA function was significantly higher in cirrhotic patients than in controls. The RA reservoir and conduit strains were significantly lower in cirrhotic patients, while there was no difference in the RA contractile strain. Early diastolic and systolic RA strain rates were significantly lower in cirrhotic patients than in controls, whereas there was no difference in the RA late diastolic strain rate between the two groups. Transaminases and bilirubin correlated negatively with RV global longitudinal strain and RV-free wall strain in patients with end-stage liver cirrhosis. The Model for End-stage Liver Disease (MELD) score, predictor of 3-month mortality, correlated with parameters of RV structure and systolic function, and RA active function in patients with end-stage liver cirrhosis. Conclusions: RA and RV remodeling is present in patients with end-stage liver cirrhosis even though RV systolic function is preserved. Liver enzymes, bilirubin, and the MELD score correlated with RV and RA remodeling.

scholarly journals Validation of a new prognostic model to predict short and medium-term survival in patients with liver cirrhosis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Tomasz Dziodzio ◽  
Robert Öllinger ◽  
Wenzel Schöning ◽  
Antonia Rothkäppel ◽  
Radoslav Nikolov ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Risk Score ◽  
Meld Score ◽  
Medium Term ◽  
Term Survival ◽  
Risk Of Death ◽  
Class B ◽  
Pugh Class ◽  
End Stage

Abstract Background MELD score and MELD score derivates are used to objectify and grade the risk of liver-related death in patients with liver cirrhosis. We recently proposed a new predictive model that combines serum creatinine levels and maximum liver function capacity (LiMAx®), namely the CreLiMAx risk score. In this validation study we have aimed to reproduce its diagnostic accuracy in patients with end-stage liver disease. Methods Liver function of 113 patients with liver cirrhosis was prospectively investigated. Primary end-point of the study was liver-related death within 12 months of follow-up. Results Alcoholic liver disease was the main cause of liver disease (n = 51; 45%). Within 12 months of follow-up 11 patients (9.7%) underwent liver transplantation and 17 (15.1%) died (13 deaths were related to liver disease, two not). Measures of diagnostic accuracy were comparable for MELD, MELD-Na and the CreLiMAx risk score as to power in predicting short and medium-term mortality risk in the overall cohort: AUROCS for liver related risk of death were for MELD [6 months 0.89 (95% CI 0.80–0.98) p < 0.001; 12 months 0.89 (95% CI 0.81–0.96) p < 0.001]; MELD-Na [6 months 0.93 (95% CI 0.85–1.00) p < 0.001 and 12 months 0.89 (95% CI 0.80–0.98) p < 0.001]; CPS 6 months 0.91 (95% CI 0.85–0.97) p < 0.01 and 12 months 0.88 (95% CI 0.80–0.96) p < 0.001] and CreLiMAx score [6 months 0.80 (95% CI 0.67–0.96) p < 0.01 and 12 months 0.79 (95% CI 0.64–0.94) p = 0.001]. In a subgroup analysis of patients with Child-Pugh Class B cirrhosis, the CreLiMAx risk score remained the only parameter significantly differing in non-survivors and survivors. Furthermore, in these patients the proposed score had a good predictive performance. Conclusion The CreLiMAx risk score appears to be a competitive and valid tool for estimating not only short- but also medium-term survival of patients with end-stage liver disease. Particularly in patients with Child-Pugh Class B cirrhosis the new score showed a good ability to identify patients not at risk of death.

The 1-year and 3-month prognostic utility of the AST/ALT ratio and model for end-stage liver disease score in patients with viral liver cirrhosis

2002 ◽  
Vol 97 (11) ◽  
pp. 2855-2860 ◽  
Author(s):  
Edoardo Giannini ◽  
Federica Botta ◽  
Emanuela Testa ◽  
Paola Romagnoli ◽  
Simone Polegato ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Disease Score ◽  
End Stage Liver Disease ◽  
Prognostic Utility ◽  
End Stage

Model for End-Stage Liver Disease Score Predicts Adverse Events Related to Ventricular Assist Device Therapy

2012 ◽  
Vol 93 (5) ◽  
pp. 1541-1548 ◽  
Author(s):  
Pramod Bonde ◽  
Natalie C. Ku ◽  
Elizabeth A. Genovese ◽  
Christian A. Bermudez ◽  
Jay K. Bhama ◽  
...  
Keyword(s):  
Liver Disease ◽  
Adverse Events ◽  
Ventricular Assist Device ◽  
Disease Score ◽  
Device Therapy ◽  
Assist Device ◽  
Ventricular Assist ◽  
End Stage Liver Disease ◽  
End Stage
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