Abstract
End-stage liver disease (ESLD) is characterized by the deterioration of liver function and a subsequent high mortality rate. Studies have investigated the use of adult stem cells to treat ESLD. Here, a systematic review and meta-analysis was conducted to determine the efficacy of a combination therapy with adult stem cell transplantation and traditional medicine for treating ESLD. Four databases—including PubMed, Web of Science, Embase, and Cochrane Library—were investigated for studies published before January 31, 2021. The main outcome indicators were liver function index, model for end-stage liver disease (MELD) scores, and Child‒Turcotte‒Pugh (CTP) scores. Altogether, 1604 articles were retrieved, of which eight met the eligibility criteria; these studies included data for 579 patients with ESLD. Combination of adult stem cell transplantation with conventional medicine significantly improved its efficacy with respect to liver function index, CTP and MELD scores, but this effect gradually decreased over time. Moreover, a single injection of stem cells was more effective than two injections with respect to MELD and CTP scores and total bilirubin (TBIL) and albumin (ALB) levels, with no significant difference in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. With respect to the TBIL levels, patients receiving mononuclear cells (MNCs) experienced a significantly greater therapeutic effect—starting from twenty-four weeks after the treatment—whereas with respect to ALB levels, CD34+ autologous peripheral blood stem cells (CD34+ APBSCs) and MNCs had similar therapeutic effects. Severe complications associated with adult stem cell treatment were not observed. Although the benefits of combination therapy with respect to improving liver function were slightly better than those of the traditional treatment alone, they gradually decreased over time.Systematic review registration: PROSPERO registration number: CRD42021238576.
Highlights
The natural course of cirrhosis is characterized by the progression from an early asymptomatic phase—termed “compensated cirrhosis”—to the development of portal hypertension and complications, with or without liver dysfunction, termed “decompensated cirrhosis” or “endstage liver disease” (ESLD) [1]
CD34+ autologous peripheral blood stem cell (APBSC), autologous peripheral blood stem cells; BM-MNCs, bone marrow mononuclear cells; hUCMSCs, human umbilical cord mesenchymal stem cells; ABMMSC, autologous bone marrow mesenchymal stromal cells; PB-MNCs, peripheral blood mononuclear cells; AC, alcoholic cirrhosis; nRCT, non-randomized control trial; randomized controlled trials (RCTs), randomized control trial; HBV, hepatitis B virus; HCV, hepatitis C virus; NA, not available; Granulocyte colony-stimulating factor (G-CSF), granulocyte colony-stimulating factor and 24 weeks post-transplantation (SMD − 0.25; 95% confidence interval (CI) − 0.46, − 0.03; P = 0.02) (Fig. 3)
With respect to the association between the species of adult stem cells and efficacy, the total bilirubin (TBIL) level (Additional file 1: Figure S5) was found to be considerably decreased in studies involving transplantation with MNCs as compared to that in other studies (CD34 + APBSC—Standardized mean difference (SMD) − 0.02; 95% CI − 0.38 to 0.35; P = 0.93; ABMMSC—SMD − 0.10; 95% CI − 0.61 to 0.40; P = 0.69; MNCs—SMD − 0.76; 95% CI − 1.28 to − 0.24; P = 0.004)
Summary
The natural course of cirrhosis is characterized by the progression from an early asymptomatic phase—termed “compensated cirrhosis”—to the development of portal hypertension and complications, with or without liver dysfunction, termed “decompensated cirrhosis” or “endstage liver disease” (ESLD) [1]. Patients with ESLD who are hospitalized in the intensive care unit (ICU) have a mortality rate of 40–80% [4–8]. Liver transplantation is the only effective treatment for ESLD [9]. The failure of liver transplantation will lead to further progressive fibrosis that will impede liver regeneration and cause irreversible cirrhosis [10, 11]. As the demand for donor liver substantially exceeds its availability, an increasing number of patients with ESLD are dying while awaiting liver transplantation; there is a need to develop strategies for alternative therapy [12, 13]
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