Late-onset acute rejection after living donor liver transplantation

AIM： TO investigate the incidence and risk factors of late-onset acute rejection （LAR） and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids. METHODS： Adult living donor liver transplantation recipients （n = 204） who survived more than 6 mo after living donor liver transplantation were enrolled. Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation, tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration. Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median follow-up period was 34 too. RESULTS： LAR was observed in 15 cases （7%） and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset post-transplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients （19%）. Multivariate analysis revealed that a cyclosporine-based regimen was significantly associated with LAR.events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.

Clostridium difficile-associated diarrhea after living donor liver transplantation

AIM： To assess the incidence and analyze the risk factors for Clostridium difficile-associated diarrhea （CDAD）after living donor liver transplantation （LDLT） in adult.METHODS： The micobiological data and medical records of 242 adult recipients that underwent LDLT at the Tokyo University Hospital were analyzed retrospectively. The independent risk factors for postoperative CDAD were identified.RESULTS： Postoperative CDAD occurred in 11 （5%）patients. Median onset of CDAD was postoperative d 19（range, 5-54）. In the multivariate analyses, male gender （odds ratio, 4.56） and serum creatinine （≥ 1.5 mg/dL,odds ratio, 16.0） independently predicted postoperative CDAD.CONCLUSION： CDAD should be considered in the differential diagnosis of patients with postoperative diarrhea after LDLT.

Efficacy of mycofenolate mofetil for steroid-resistant acute rejection after living donor liver transplantation

AIM： To discuss the use of mycophenolate mofetil （MMF） as an immunosuppressant in steroid resistant rejection after liver transplantation. METHODS： The clinical records of 260 adult patients who underwent living donor liver transplantation （LDLT） were reviewed. Tacrolimus and methylprednisolone were used for primary immunosuppression. Acute rejection was first treated with steroids. When steroid resistance occurred, the patient was treated with a combination of steroids and MMF. Anti-T-cell monoclonal antibody was administered to patients who were not responsive to steroids in combination with MMF.RESULTS： A total of 90 （35%） patients developed acute rejection. The median interval time from transplantation to the first episode was 15 d. Fifty-four patients were steroid resistant. Forty-four patients were treated with MMF and the remaining 10 required anti-T-cell monoclonal antibody treatment. Progression to chronic rejection was observed in one patient. Bone marrow suppression and gastrointestinal symptoms were the most common side effects associated with MMF use. There was no significant increase in opportunistic infections. CONCLUSION： Our results demonstrate that MMF is a potent and safe immunosuppressive agent for rescue therapy in patients with acute rejection after LDLT.

Liver transplantation in HCV/HIV positive patients

Since the introduction of highly active antiretroviral therapy (HAART) in 1996 for human immunodeficiency virus (HIV)-infected patients, the incidence of liver diseases secondary to co-infection with hepatitis C has increased. Although data on the outcome of liver transplantation in HIV-infected recipients is limited, the overall results to date seem to be comparable to that in non-HIV-infected recipients. Liver transplant centers are now accepting HIV-infected individuals as organ recipients. Post-transplantation HIV replication is controlled by HAART. Hepatitis C re-infection of the liver graft, however, remains an important problem because cirrhotic changes of the liver graft may be more rapid in HIV-infected recipients. Interactions between the HAART components and immunosuppressive drugs influence drug metabolism and therefore meticulous monitoring of drug blood level concentrations is required. The risk of opportunistic infection in HIV-positive transplant patients seems to be similar to that in HIV-negative transplant recipients.

Recurrence of cholestatic liver disease after living donor liver transplantation

End-stage liver disease, due to cholestatic liver diseases with an autoimmune background such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), is considered a good indication for liver transplantation. Excellent overall patient and graft outcomes, based mostly on the experience from deceased donor liver transplantation (DDLT), have been reported. Due to the limited number of organ donations from deceased donors in most Asian countries, living donor liver transplantation (LDLT) is the mainstream treatment for end-stage liver disease, including that resulting from PBC and PSC. Although the initial experiences with LDLT for PBC and PSC seem satisfactory or comparable to that with DDLT, some aspects, including the timing of transplantation, the risk of recurrent disease, and its long-term clinical implications, require further evaluation. Whether or not the long-term outcomes of LDLT from a biologically related donor are equivalent to that of DDLT requiresfurther observations. The clinical course following LDLT may be affected by the genetic background shared between the recipient and the living related donor.

Perceptions of post-transplant recidivism in liver transplantation for alcoholic liver disease

Although alcoholic liver disease(ALD) is regarded as a common indication for liver transplantation(LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD.