Safety Assessment of Autologous Stem Cell Combination Therapy in Patients With Decompensated Liver Cirrhosis: A Pilot Study.

BACKGROUND: Haematopoietic stem cell (HSC) infusion has demonstrated short-term improvement in liver functions in patients with chronic liver disease. The combination of HSC with mesenchymal stem cells (MSCs), which has an immunomodulatory effect, may augment the effects and enhance the duration of improvements on liver functions. The aim of the present study was to assess the safety of infusing the combination of autologous HSCs and MSCs in decompensated liver cirrhosis. METHODS: In phase I of the study, in vitro assessment was performed to observe the effect of coculturing MSCs with HSCs on their viability and cytokine profiles. Phase II of the study was to assess the safety of combination of stem cell infusions. Bone marrow (50 ml) was aspirated for MSC isolation and expansion using standard protocol. Patients received subcutaneous doses (n = 5) of granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization followed by leukapheresis for harvesting HSCs using CliniMacs. HSCs and MSCs were infused through the hepatic artery under fluoroscopic guidance and were monitored for any adverse effects. RESULTS: In vitro studies revealed 94% viable HSCs in coculture similar to monoculture. HSCs released only interleukin (IL)-8, whereas MSCs secreted IL-8 and IL-6 in monocultures, and both IL-8 and IL-6 were secreted in coculture. G-CSF administration- and bone marrow aspiration-related complications were not observed. Infusion of the cells through the hepatic artery was safe, and no postprocedural complications were noted. CONCLUSION: The combination of autologous HSC and MSC infusion is a safe procedure in patients with decompensated liver cirrhosis, and the outcomes needed to be assessed in larger studies. TRIAL NUMBER: NCT04243681.

Budd-Chiari syndrome: outcomes of endovascular intervention-A single-center experience.

AIM: Outcomes of endovascular intervention in Budd-Chiari syndrome (BCS) have been reported with varied results. Clinical outcomes of endovascular interventions in BCS and role of various prognostic scores were critically evaluated in this study. METHODS: This study retrospectively analyzed consecutive patients of BCS who underwent endovascular intervention between January 2007 and May 2016 at our center. Technical, clinical successes and complications were documented. The role of the prognostic scores such as Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), Rotterdam index, and original Clichy score in predicting mortality, clinical success, and need for re-interventions were also assessed. RESULTS: A total of 88 patients were analyzed. The median follow up was 12 months (range 1-96 months). Thirteen (14.8%) patients had combined inferior vena cava (IVC) and hepatic vein (HV) obstruction; HV obstruction in 33 (37.5%) and inferior vena cava IVC obstruction in 42 (47.7%) patients. The following interventions were done: IVC angioplasty alone (n = 11), IVC angioplasty with stenting (n = 36), HV angioplasty with stenting (n = 26), combined HV and IVC stent (n = 2), and direct intrahepatic porto-systemic shunt (DIPS) (n = 13). Overall technical success was 87/88 (98.86%), and clinical success was 76/88 (86.36%). Immediate complications were noted in 8 patients (10%). The 1-, 2-, 3-, and 4-year stent patency rates were 90.91%, 81.08%, 74.59%, and 70.45%, respectively. Re-interventions were required in 15 (17%). Overall mortality was 6 (6.8%). Apart from MELD >14, none of the other prognostic score could predict mortality, clinical success, and need for re-interventions. CONCLUSION: Endovascular interventions play an important role in the management of BCS, in properly selected patients, even if prognostic score is unfavorable.

Autologous mobilized peripheral blood CD34(+) cell infusion in non-viral decompensated liver cirrhosis.

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.