Published online Jun 21, 2015. doi: 10.3748/wjg.v21.i23.7264
Peer-review started: December 29, 2014
First decision: January 22, 2015
Revised: February 3, 2015
Accepted: March 19, 2015
Article in press: March 19, 2015
Published online: June 21, 2015
Processing time: 175 Days and 2.3 Hours
AIM: To study the effect of mobilized peripheral blood autologous CD34 positive (CD34+) cell infusion in patients with non-viral decompensated cirrhosis.
METHODS: Cirrhotic patients of non-viral etiology were divided into 2 groups based on their willingness to be listed for deceased donor liver transplant (DDLT) (control, n = 23) or to receive autologous CD34+ cell infusion through the hepatic artery (study group, n = 22). Patients in the study group were admitted to hospital and received granulocyte colony stimulating factor injections 520 μg/d for 3 consecutive days to mobilize CD34+ cells from the bone marrow. On day 4, leukapheresis was done and CD34+ cells were isolated using CliniMAC magnetic cell sorter. The isolated CD34+ cells were infused into the hepatic artery under radiological guidance. The patients were discharged within 48 h. The control group received standard of care treatment for liver cirrhosis and were worked up for DDLT as per protocol of the institute. Both groups were followed up every week for 4 wk and then every month for 3 mo.
RESULTS: In the control and the study group, the cause of cirrhosis was cryptogenic in 18 (78.2%) and 16 (72.72%) and alcohol related in 5 (21.7%) and 6 (27.27%), respectively. The mean day 3 cell count (cells/μL) was 27.00 ± 20.43 with a viability of 81.84 ± 11.99%. and purity of 80%-90%. Primary end point analysis revealed that at 4 wk, the mean serum albumin in the study group increased significantly (2.83 ± 0.36 vs 2.43 ± 0.42, P = 0.001) when compared with controls. This improvement in albumin was, however, not sustained at 3 mo. However, at the end of 3 mo there was a statistically significant improvement in serum creatinine in the study group (0.96 ± 0.33 vs 1.42 ± 0.70, P = 0.01) which translated into a significant improvement in the Model for End-Stage Liver Disease score (15.75 ± 5.13 vs 19.94 ± 6.68, P = 0.04). On statistical analysis of secondary end points, the transplant free survival at the end of 1 mo and 3 mo did not show any significant difference (P = 0.60) when compared to the control group. There was no improvement in aspartate transaminase, alanine transaminase, and bilirubin at any point in the study population. There was no mortality benefit in the study group. The procedure was safe with no procedural or treatment related complications.
CONCLUSION: Autologous CD 34+ cell infusion is safe and effectively improves liver function in the short term and may serve as a bridge to liver transplantation.
Core tip: Cirrhosis of the liver is a chronic progressive disease with high morbidity and mortality without liver transplantation. Alternative stem cell based therapies have shown promising results. In our study, we used autologous CD34 positive (CD34+) cell infusion in decompensated cirrhotic patients of non-viral etiology. This is the first study which has compared these patients with controls who were selected from a waiting list of liver transplantation candidates. The results shows improvement in albumin at 1 mo and Model for End-Stage Liver Disease score at 3 mo. Though many questions still remain unanswered, stem cell therapy is a promising treatment modality and serves currently as a bridge to liver transplantation.