[Stage 2 Cirrhosis] Changes in Liver Fibrosis Following Hepatic Artery Injection of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Patients with Alcoholic Cirrhosis

Research Summary

Study Results

Patients with alcoholic cirrhosis who had abstained from alcohol for at least 6 months received two injections of mesenchymal stem cells cultured from their own bone marrow into the hepatic artery. The primary endpoint was improvement in the fibrosis grade (Laeneck score), which indicates the degree of liver fibrosis.

A biopsy performed 12 weeks after the second administration showed that the fibrosis grade had improved in 6 out of 11 patients (54.5%) (P = 0.020). The area occupied by collagen decreased from 22.6% (±8.4) to 17.7% (±6.9) (P < 0.001). The expression of TGF-β1, type I collagen, and α-SMA—markers associated with fibrosis—also decreased (P < 0.05). The Child-Pugh score, a marker of liver function, improved in 10 patients (90.9%) (P < 0.001). However, there were no differences in AST, ALT, total bilirubin, or platelet counts before and after treatment.

All 11 patients tolerated the treatment course. Although fever, hypersensitivity reactions, and acute rejection were observed, there were no serious complications or adverse reactions, and no tumors related to the cell therapy were identified.

Figure. Changes in the percentage of collagen area in liver tissue before and after treatment. Original Figure 2G, Liver Int.

Study Design

This was an open-label, single-arm Phase 2 clinical trial conducted at a tertiary general hospital in Korea from May 2010 to January 2011 (ClinicalTrials.gov NCT01741090). Twelve patients aged 37–60 years with alcohol-related cirrhosis confirmed by biopsy and who had abstained from alcohol for at least 6 months were enrolled; one patient was excluded due to alcohol consumption, leaving 11 patients (10 men, 1 woman) included in the final analysis. No control group was included.

Secondary endpoints included changes in the Child-Pugh score, fibrosis-related markers, and adverse events. Liver biopsies were performed twice—before administration and 12 weeks after the second dose—and were interpreted by two pathologists who were blinded to patient information. Alcohol consumption was verified weekly via telephone and monthly through in-person interviews.

Cells Used and Administration Method

Autologous bone marrow-derived mesenchymal stem cells obtained from the patients’ own bone marrow were used. After local anesthesia, 10–20 mL of bone marrow was harvested from the posterior region of the ilium and cultured in a GMP facility for approximately one month to achieve 4–5 passages. The release criteria were a viability rate of 80% or higher, negative for microbial contamination, at least 90% of cells positive for CD73 and CD105, and less than 3% of cells positive for CD14, CD34, and CD45.

The dosage was 5 × 10⁷ cells per administration, mixed with 10 mL of saline solution and administered twice—at 4 weeks and 8 weeks. A thin catheter was inserted into the right hepatic artery to infuse the cells; for the second administration, frozen cells were thawed and used.

Discussion

This study demonstrates that in patients with alcoholic cirrhosis who had abstained from alcohol for at least 6 months, two intra-hepatic arterial injections of autologous bone marrow-derived mesenchymal stem cells resulted in changes in the degree of liver fibrosis and liver function markers. In the remaining 5 patients, the fibrosis grade remained unchanged.

There are clear limitations. Since the study was conducted at a single institution with only 11 participants and no control group, it is impossible to distinguish whether the observed changes were due to the cell administration or the natural course of maintaining abstinence. The research team stated that it was ethically difficult to perform repeated biopsies on the control group. Since a biopsy involves removing only a portion of the liver, there is a margin of error depending on the site of collection. The researchers did not track the migration path of the injected cells within the body, and the observation period was limited to 12 weeks. The cells used in this study were manufactured by FCB-Pamisell, and the research was funded by the Ministry of Health and Welfare’s R&D program.