Combination Treatments of Plasma Exchange and Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation for Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure: A Clinical Trial in China

Abstract

Background. Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a common type of liver failure with a high mortality. This study aimed at investigating the safety and efficacy of the combination treatment of plasma exchange (PE) and umbilical cord-derived mesenchymal stem cell (UC-MSCs) transplantation for HBV-ACLF patients.Methods. A total of 110 HBV-ACLF patients treated in our hospital from January 2012 to September 2017 were enrolled into this trial and divided into the control group (n=30), UC-MSC group (n=30), PE group (n=30), and UC-MSC + PE group (n=20) based on their treatments. The hepatic function, coagulation, and virological and immunological markers were assessed at baseline and 30, 60, 90, 180, and 360 days. The endpoint outcomes were death and unfavorable outcome (need for liver transplantation or death).Results. The UC-MSC + PE group had the lowest rates of death and unfavorable outcome at 30 days, 60 days, and 90 days posttreatment among the four groups, but the difference did not reach significances. The multivariate logistic regression analysis demonstrated that hemoglobin, prothrombin activity, and MELD (model for end-stage liver disease) score were the independent factors associated with the unfavorable outcome (allP<0.05). The levels of total bilirubin, alanine aminotransferase, aspartate transaminase, and MELD score were significantly decreased during treatments (allP<0.05).Conclusion. UC-MSCs combined with PE treatment had good safety but cannot significantly improve the short-term prognosis of HBV-ACLF patients with as compared with the single treatment. The long-term efficacy should be further evaluated. This trial is registered with registration no.NCT01724398.

Exosomes Derived From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Acetaminophen-induced Acute Liver Failure Through Activating ERK and IGF-1R/PI3K/AKT Signaling Pathways

“…Recently, hUCMSCs, which are multipotent stem cells derived from umbilical cord, have emerged as a promising candidate to develop innovative therapeutic treatment for ALF due to their ability to secrete many damage repair factors [35][36][37]. In the present study, we found that hUCMSCs can be esaily isolated from the donor's umbilical cord without ethical concerns and showed broblast-like morphology.…”

Therapeutic effect and safety of stem cell therapy for chronic liver disease: a systematic review and meta-analysis of randomized controlled trials

“…We found substantial heterogeneity at most of the time points (I 2 = 54-90%). By excluding the results of Lin et al [23] at week 2, Salama et al [21] at week 4, Xu et al [43] at week 8, and Shi et al [24] at week 48, sensitivity analyses showed lowered heterogeneity among the remaining studies (Additional file 2: Table S2). Publication bias was evaluated at weeks 4, 12, and 24, and the funnel plot and Egger's test indicated no evident publication bias (Additional file 3 Fig.…”

Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration

“…Mesenchymal cell populations isolated from the afterbirth tissues are well characterized in terms of their positive pleiotropic effect in the treatment of liver failure in animals (Tables 7 and 8) and in humans [154,155].…”

“…twice or four times, depending on the group) were administered to patients with acute hepatic failure overlapping chronic failure caused by HBV infection. The decrease in ALAT, ASPAT and bilirubin in plasma, as well as in MELD score, was observed[154]. In the pilot study of Shi et al, patients after liver transplantation…”