Does MMF really slow down fibrosis of HCV recurrence in liver transplant recipients?

Abstract

We read with interest the study by Manzia et al. [1] onthe effect of maintenance of mycophenolate mofetil(MMF) monotherapy on progression of recurrent hepati-tis C virus (HCV) after liver transplantation.The authors concluded: MMF ‘‘monotherapy may cur-rently represent the preferred immunosuppressive alterna-tive for the long-term management of liver transplantrecipients with HCV infection’’. However, we believe thatthey should exert great caution in coming to this conclu-sion, as their results [1] have not been properly evaluatedwithin the context of the complete picture of the pub-lished literature on the subject.Our group recently published a review on the role ofMMF and azathioprine in liver transplantation withregard to acute rejection, renal dysfunction and HCVrecurrence [2]. Considering HCV recurrence, we showedthat between 2001 and 2007, 17 studies evaluated MMFand HCV recurrence; among these, only two studies [3,4]found a decreased severity of HCV recurrence with MMFand one of these had no multivariate analysis [3] – citedby Manzia et al. Nine studies (reported in reference 2)documented similar severity of HCV recurrence; however,six studies [5–10] showed increased severity of HCVrecurrence, but only one of these [10] was cited byManzia et al.Therefore, the study by Manzia et al. [1] representsonly the third study out of 18 (17%) showing a beneficialtherapeutic effect of MMF on HCV progression after livertransplantation, whereas 33% shows a deleterious effect.For this reason, in omitting to cite this literature, Maniaet al. have gone against the available evidence in statingthat MMF is the preferred immunosuppressive alternativefor long-term regimen in patients transplanted for HCV-related cirrhosis.Moreover, although Manzia et al. [1] showed in theirpatient cohort a positive association between a favorableeffect of MMF monotherapy on the progression of hepa-tic fibrosis in HCV liver transplant patients, there are sev-eral methodological issues. There was no multivariateanalysis evaluating MMF with respect to fibrosis progres-sion. This is especially important, as the study was retro-spective and nonrandomized and with only 15 patientsper arm. Although other studies have also been retrospec-tive and nonrandomized [2], several have included multi-variate analyses.Thus, overall, the current published evidence for MMFwith respect to the severity of fibrosis and HCV recur-rence does not suggest a beneficial effect. If anything, apotential adverse effect is shown as we pointed out in ourreview [2], although we acknowledged then, and now thatthe evidence is weak.Giacomo Germani,