To the Editor:

We read with interest the article by Peng et al. investigating the potential beneficial effects of culture expanded autologous mesenchymal stem cells (MSCs) in patients with liver failure caused by hepatitis B virus (HBV).1 Though it is reassuring that MSC therapy delivered via the hepatic artery in this group of patients appears to be safe and feasible, there are several areas of the article that would benefit from clarification.

It would be helpful if the investigators could provide data regarding HBV viral load, genotype, and E antigen status for each patient in the trial, as they are important risk factors for progressive liver disease and hepatocellular carcinoma.2, 3 These data, in addition to hepatitis C virus coinfection, are required before robust conclusions about the efficacy of MSC therapy can be made.

Patients on antiviral treatment were excluded from the trial. We would like the investigators to clarify whether HBV antiviral therapy was given at any time to the enrolled patients. This is of importance, because the efficacy of antiviral therapy in this patient group has been well established for over a decade.4, 5 In contrast, the antiviral, antifibrotic, and regenerative effects of MSCs have not been proven.6

Furthermore, the surface expression of cluster of differentiation (CD)73, CD90, CD105, and evidence of trilineage differentiation, which are required to define a pure MSC population, have not been provided.7 The article would benefit from inclusion of such data, because culture-expanded MSCs are frequently heterogeneous and can contain contaminating cells.8

In summary, we feel additional data are required before firm conclusions about the efficacy of MSC therapy in HBV liver failure can be made. Moreover, MSC therapy should only be considered after an optimization of antiviral therapy in future clinical trials.


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  • 1
    Peng L, Xie DY, Lin BL, Liu J, Zhu HP, Xie C, et al. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: short-term and long-term outcomes. HEPATOLOGY 2011; 53: 820828.
  • 2
    Chen CJ, Yang HI, Iloeje UH; REVEAL-HBV Study Group. Hepatitis B virus DNA levels and outcomes in chronic hepatitis B. HEPATOLOGY 2009; 49: S72-S84.
  • 3
    Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002; 347: 168-174.
  • 4
    Lok ASF, McMahon BJ. Chronic hepatitis B: update 2009. HEPATOLOGY 2009; 50: 661-662.
  • 5
    Yao FY, Terrault NA, Freise C, Maslow L, Bass NM. Lamivudine treatment is beneficial in patients with severely decompensated cirrhosis and actively replicating hepatitis B infection awaiting liver transplantation: a comparative study using a matched, untreated cohort. HEPATOLOGY 2001; 34: 411-416.
  • 6
    Houlihan DD, Newsome PN. Critical review of clinical trials of bone marrow stem cells in liver disease. Gastroenterology 2008; 135: 438-450.
  • 7
    Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317.
  • 8
    Prockop DJ, Olson SD. Clinical trials with adult stem/progenitor cells for tissue repair: let's not overlook some essential precautions. Blood 2007; 109: 3147-3151.

Diarmaid D. Houlihan* †, Laurence J. Hopkins*, Shankar X. Suresh*, Matthew J. Armstrong* †, Philip N. Newsome* †, * Center for Liver Research, National Institute for Health Research, University of Birmingham, Birmingham, UK, † Liver Unit, Queen Elizabeth Hospital, University Hospital Birmingham National Health Service Foundation Trust Birmingham, UK.