Abstract
We read with great interest the article by Khan et al. (1), who showed that patients with chronic liver disease due to alcohol consumption can significantly improve within a 6-month period after being treated with a single intrahepatic injection of EpCAM+ fetal liver cells. As we are involved in a clinical trial on fetal liver cell infusion in patients with chronic liver disease (http://clinicaltrials.gov/ct2/show/NCT01013194?term=fetal+liver+trial+cirrhosis&rank=1), there are some observations we would like to share concerning this article.
The fetuses used in Khan et al.'s study were between the 16th and 20th weeks, and the total cellular yield reported was 8 × 109 (there are no data on the cellular yield of each fetus). These data are surprisingly different from those reported by the same group in a previous article, where the total number of cells obtained ranged between 140.0 ± 30.8 × 106 (15–20 weeks) and 193.4 ± 96.8 × 106 (21–25 weeks), depending on the gestational week (2). Based on our data, we can confirm that the cellular yield of fetuses between the 17th and 22nd weeks can range between 3 × 108 and 3.3 × 109 (unpublished data).
Patients with alcoholic liver disease can improve clinically over a 6-month period with abstention from alcohol. In order to confirm a correlation between cellular therapy and clinical improvement, the treated patients the study by Dr. Habibullah and colleagues should have been randomized with untreated controls.
A positive hepatic scintigraphy after cellular transplantation cannot be considered proof of engraftment or definitive homing of cells, but can rule out extrahepatic shunting. We know that it is difficult to track infused cells and follow their long-term engraftment by radio labeling, yet we believe the most advisable approach to assessing liver regeneration after implantation is still liver histology through a transjugular liver biopsy in compromised patients. Regarding clinical improvement soon after cellular infusion, it would be interesting to know if the patient treated in 2007, as shown in Figure 5 of the article (1), experienced further general improvement or needed to undergo liver transplantation.
Finally, we strongly believe that for confirmation of the therapeutic efficacy of fetal liver cell transplantation in patients with chronic liver disease a randomized controlled trial should be conducted in order to avoid bias and misinterpretation of published outcomes.