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Published on: October 10, 2011
Autologous mobilized peripheral blood CD34(+) cell infusion in non-viral decompensated liver cirrhosis
Mithun Sharma1, Padaki Nagaraja Rao1, Mitnala Sasikala1
1Mithun Sharma, Padaki Nagaraja Rao, Vardaraj Gokak, BPSS Raju, D Nageshwar Reddy, Department of Gastroenterology and Hepatology, Asian Institute of Gastroenterology, Asian Healthcare Foundation, Hyderabad 500082, India.
Insights
Autologous CD 34(+) cell infusion safely improved liver function in patients with non-viral decompensated cirrhosis in the short term. This innovative therapy may serve as a bridge to liver transplantation.
Area of Science:
- Hepatology
- Regenerative Medicine
- Cell Therapy
Background:
- Non-viral decompensated cirrhosis significantly impacts liver function and patient prognosis.
- Liver transplantation is a definitive treatment, but donor organ availability is limited.
- Exploring alternative therapeutic strategies is crucial for managing cirrhotic patients.
Purpose of the Study:
- To evaluate the efficacy and safety of autologous CD34(+) cell infusion in patients with non-viral decompensated cirrhosis.
- To assess the impact of this cell therapy on liver function markers and clinical outcomes.
- To determine its potential as a bridge to deceased donor liver transplantation (DDLT).
Main Methods:
- Patients with non-viral decompensated cirrhosis were divided into a control group (n=23) and a study group (n=22).
- The study group received autologous CD34(+) cell infusion via the hepatic artery after mobilization with granulocyte colony-stimulating factor and leukapheresis.
- Both groups were followed for 3 months, with assessments of liver function, renal function, and transplant-free survival.
Main Results:
- The study group showed a significant short-term increase in serum albumin at 4 weeks (P=0.001) and improved serum creatinine at 3 months (P=0.01).
- Model for End-Stage Liver Disease (MELD) scores significantly improved in the study group at 3 months (P=0.04).
- No significant difference in transplant-free survival or improvements in liver enzymes (AST, ALT, bilirubin) was observed between groups; the procedure was safe.
Conclusions:
- Autologous CD34(+) cell infusion is a safe procedure for non-viral decompensated cirrhosis.
- The therapy demonstrates short-term improvements in liver function, particularly albumin and creatinine levels.
- CD34(+) cell infusion may serve as a potential bridge therapy to liver transplantation.
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.
