title: Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial.
abstract: Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been suggested as an effective therapy for liver cirrhosis. The efficacy and safety of autologous BM-MSC transplantation in the treatment of alcoholic cirrhosis were investigated. Seventy-two patients with baseline biopsy-proven alcoholic cirrhosis who had been alcohol-abstinent for more than 6 months underwent a multicenter, randomized, open-label, phase 2 trial. Patients were randomly assigned to three groups: one control group and two autologous BM-MSC groups that underwent either one-time or two-time hepatic arterial injections of 5 × 107BM-MSCs 30 days after BM aspiration. A follow-up biopsy was performed 6 months after enrollment, and adverse events were monitored for 12 months. The primary endpoint was improvement in fibrosis quantification based on picrosirius red staining. The secondary endpoints included liver function tests, Child-Pugh score, and Model for End-stage Liver Disease score. Outcomes were analyzed by per-protocol analysis. In terms of fibrosis quantification (before versus after), the one-time and two-time BM-MSC groups were associated with 25% (19.5 ± 9.5% versus 14.5 ± 7.1%) and 37% (21.1 ± 8.9% versus 13.2 ± 6.7%) reductions in the proportion of collagen, respectively (P < 0.001). In the intergroup comparison, two-time BM-MSC transplantation in comparison with one-time BM-MSC transplantation was not associated with improved results in fibrosis quantification (P > 0.05). The Child-Pugh scores of both BM-MSC groups (one-time 7.6 ± 1.0 versus 6.3 ± 1.3 and two-time 7.8 ± 1.2 versus 6.8 ± 1.6) were also significantly improved following BM-MSC transplantation (P < 0.05). The proportion of patients with adverse events did not differ among the three groups.
  
  
  
  Autologous BM-MSC transplantation safely improved histologic fibrosis and liver function in patients with alcoholic cirrhosis. (Hepatology 2016;64:2185-2197).
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea.
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Suk
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju College of Medicine, Wonju, South Korea.
authors.forename: Moon Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Uijeongbu St Mary's Hospital College of Medicine, The Catholic University, Uijeongbu, South Korea.
authors.forename: Chang Wook
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Ja Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Bundang CHA Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Bundang CHA Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea.
authors.forename: Dong Joon
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, South Korea.
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, South Korea.
authors.forename: Sae Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, South Korea.
authors.forename: Hong Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, South Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, College of Medicine & Hospital, Catholic University of Daegu, Daegu, South Korea.
authors.forename: Chang-Hyeong
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, College of Medicine & Hospital, Catholic University of Daegu, Daegu, South Korea.
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju College of Medicine, Wonju, South Korea.
authors.forename: Yoon Ok
authors.initials: YO
authors.lastname: Jang
authors.affiliation: Department of Pathology, Wonju Severance Christian Hospital, Yonsei University, Wonju College of Medicine, Wonju, South Korea.
authors.forename: Mee Yon
authors.initials: MY
authors.lastname: Cho
authors.affiliation: Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University, Seoul, South Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jung
authors.affiliation: Phamicell Co., Ltd, Sungnam, South Korea.
authors.forename: Yong Man
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University, Seoul, South Korea.
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju College of Medicine, Wonju, South Korea.
authors.forename: Soon Koo
authors.initials: SK
authors.lastname: Baik
mesh_terms: D005260:Female; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008875:Middle Aged; D014182:Transplantation, Autologous