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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 .

Background and Aims: Long-term data on cell-based therapies, including hematopoietic stem cell infusion in cirrhosis, are sparse and lacking. Methods: Patients with cirrhosis of non-viral etiology received either standard-of-care (n = 23) or autologous CD34+ cell infusion through the hepatic artery (n = 22). Study patients received granulocyte colony-stimulating factor (commonly known as G-CSF) injections at 520 µgm per day for 3 days, followed by leukapheresis and CD34+ cell infusion into the hepatic artery. The Control group received standard-of-care treatment. Results: Mean CD34+ cell count on the third day of G-CSF injection was 27.00 ± 20.43 cells/µL 81.84 ± 11.99 viability and purity of 80-90%. Significant improvement in the model of end-stage liver disease (commonly known as MELD) score (15.75 ± 5.13 vs. 19.94 ± 6.68, p = 0.04) was noted at end of 3 months and 1 year (15.5 ± 5.3 vs. 19.8 ± 6.4, p = 0.04) but was not statistically different at end of the second (17.2 ± 5.5 vs. 20.3 ± 6.8, p = 0.17) and third-year (18.4 ± 6.1 vs. 21.3 ± 6.4, p = 0.25). No difference in mortality (6/23 vs. 5/23) was noted. Conclusions: Autologous CD34+ cell infusion effectively improved liver function and MELD score up to 1 year but the sustained benefit was not maintained at the end of 3 years, possibly due to ongoing progression of the underlying disease.

A significant proportion of patients with non-alcoholic fatty liver disease (NAFLD) in Asian sub-continent are non-overweight and may have different underlying risk factors, lifestyles and metabolic profiles. Seven hundred fifty patients of NAFLD with raised alanine-amino-transferase (ALT) were divided into non-overweight and obese group based on their body mass index (BMI). Detailed dietary and lifestyle history were obtained through questionnaires and a detailed assessment of metabolic profile and liver stiffness was done. Normal BMI ( 2 were significantly higher in obese group (4.1 ± 0.36 vs. 2.0 ± 0.15 p = 0.001). Insulin resistance and dyslipidemia were prevalent in 12% and 25% non-overweight patients respectively. Metabolic syndrome was more common in obese subjects. In addition, magnetic resonance elastography showed higher mean liver fat in the obese group with similar hepatic fibrosis. Non-overweight patients with NAFLD had lower insulin resistance and prevalence of dyslipidaemia at similar dietary and exercise pattern.