Mycophenolate mofetil combination therapy improves long‐term outcomes after liver transplantation in patients with and without hepatitis C

Wiesner, Russell H.; Shorr, Jolene; Steffen, Bettina J.; Chu, Alice; Gordon, Robert D.; Lake, John R.

doi:10.1002/lt.20453

Cited by 114 publications

(78 citation statements)

References 23 publications

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“…Six-month creatinine could be used to evaluate recipient outcomes after treatments given to recipients in the peritransplant period. Other investigators (26)(27)(28)(29) have linked databases from trials to the OPTN database for the purpose of ascertaining post-trial outcomes. For example, Brennan and colleagues (27,28) used OPTN mortality data to evaluate long-term effects of antibody induction therapy on recipients of kidney transplants, whereas Wiesner and colleagues (26,29) estimated late acute rejection for recipients of liver transplants who received mycophenolate mofetil.…”

Section: Discussionmentioning

confidence: 99%

Validating Early Post–Transplant Outcomes Reported for Recipients of Deceased Donor Kidney Transplants

Potluri

Parikh

Hall

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives Data reported to the Organ Procurement and Transplantation Network (OPTN) are used in kidney transplant research, policy development, and assessment of center quality, but the accuracy of early post-transplant outcome measures is unknown.Design, setting, participants, & measurements The Deceased Donor Study (DDS) is a prospective cohort study at five transplant centers. Research coordinators manually abstracted data from electronic records for 557 adults who underwent deceased donor kidney transplantation between April of 2010 and November of 2013. We compared the post-transplant outcomes of delayed graft function (DGF; defined as dialysis in the first posttransplant week), acute rejection, and post-transplant serum creatinine reported to the OPTN with data collected for the DDS.Results Median kidney donor risk index was 1.22 (interquartile range [IQR], 0.97-1.53). Median recipient age was 55 (IQR, 46-63) years old, 63% were men, and 47% were black; 93% had received dialysis before transplant. Using DDS data as the gold standard, we found that pretransplant dialysis was not reported to the OPTN in only 11 (2%) instances. DGF in OPTN data had a sensitivity of 89% (95% confidence interval [95% CI], 84% to 93%) and specificity of 98% (95% CI, 96% to 99%). Surprisingly, the OPTN data accurately identified acute allograft rejection in only 20 of 47 instances (n=488; sensitivity of 43%; 95% CI, 17% to 73%). Across participating centers, sensitivity of acute rejection varied widely from 23% to 100%, whereas specificity was uniformly high (92%-100%). Six-month serum creatinine values in DDS and OPTN data had high concordance (n=490; Lin concordance correlation =0.90; 95% CI, 0.88 to 0.92).Conclusions OPTN outcomes for recipients of deceased donor kidney transplants have high validity for DGF and 6-month allograft function but lack sensitivity in detecting rejection. Future studies using OPTN data may consider focusing on allograft function at 6 months as a useful outcome.

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Section: Discussionmentioning

confidence: 99%

Validating Early Post–Transplant Outcomes Reported for Recipients of Deceased Donor Kidney Transplants

Potluri

Parikh

Hall

et al. 2016

Clinical Journal of the American Society of Nephrology

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“…3,76 An analysis from United Network of Organ Sharing/Scientific Registry of Transplant Recipients (UNOS/SRTR) database suggests that addition of MMF to TAC-based regimen is associated with improved long-term outcomes after LT in patients with and without HCV. 77 A randomized, multicenter trial conducted in Japan (N575) comparing TAC plus MMF to TAC plus steroids in HCV+ recipients of living donor LT has reported similar outcomes (survival, ACR, recurrent HCV and HCC) at five years in the two groups. 78 mTOR inhibitors, such as sirolimus and everolimus, have anti-proliferative, anti-inflammatory, and possible antiviral effects, which may translate to a lower rate of HCV disease evolving to cirrhosis.…”

Section: Immunosuppressive Regimensmentioning

confidence: 99%

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Bunchorntavakul¹,

Reddy²

2014

JCTH

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Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/ progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.

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“…No beneficial effect of antibodies against interleukin-2 on HCV infection could be confirmed definitely [23]. There are contradictory data in the literature concerning a correlation between the administration of mycophenolate mofetil (MMF) -an inosine monophosphate dehydrogenase (IMPDH) inhibitor -and recurrent HCV infection [24,25]. The effect of sirolimus, given to patients with renal impairment caused by calcineurin inhibitors, on the recurrence of HCV infection is currently being investigated in several centres.…”

Section: Effect Of Immunosuppressive Therapy On Recurrent Hcv Infectionmentioning

confidence: 99%

Treatment of recurrent hepatitis C virus infection in patients after liver transplantation

Lengyel¹,

Tulassay²

2009

Clinical and Experimental Medical Journal

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The main indication for liver transplantation is the final stage of hepatic cirrhosis developed due to hepatitis C virus (HCV) infection. The recurrence of HCV infection after transplantation is a common situation. Recurrent hepatitis C is a progressive disease; in 20% of patients it produces liver cirrhosis without treatment beside immunosuppression within 5 years. Treatment of recurrent HCV infection is the most important factor of survival in patients with transplantation. Based on literary data and their observations, the authors review the factors influencing the progression of recurrent HCV infection. They discuss in details the effect of immunosuppressive therapy, the importance of selecting appropriate immunosuppressive drugs. They review the key points in the diagnosis of recurrent hepatitis C; underline the decisive role of liver biopsy carried out according to protocol in the diagnosis, as well as the hard consultation between specialists of pathology, hepatology and surgery. They demonstrate their observations with the treatment of patients on the waiting list, the results of early pre-emptive treatment of recurrent chronic hepatitis, furthermore treatment modalities and results in patients with histologically proven chronic hepatitis C. The drug of choice for chronic hepatitis C after transplantation is combined therapy with pegylated interferon and ribavirin. This therapy is able to assure sustained virological negativity in 20-50% of patients. In virus-free patients the inflammatory activity in the liver significantly decreases, and the histologic activity index improves. There are data showing a fibrosis-inhibiting effect of the treatment, however, multicentric studies are required for their confirmation. No advantage of early antiviral treatment without histologic alteration has been confirmed by most of the trials. In this group of patients common side effects of the treatment include anaemia and neutropenia, and therefore administration of erythropoietin and granulocyte stimulating factor is recommended. Further research and clinical studies are required in order to establish optimal treatment of patients with recurrent hepatitis C, to determine the dosage of pegylated interferon and ribavirin, to decrease duration of therapy, to reduce side effects and finally to achieve the healing phase in a greater percentage of patients.

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Mycophenolate mofetil combination therapy improves long‐term outcomes after liver transplantation in patients with and without hepatitis C

Cited by 114 publications

References 23 publications

Validating Early Post–Transplant Outcomes Reported for Recipients of Deceased Donor Kidney Transplants

Validating Early Post–Transplant Outcomes Reported for Recipients of Deceased Donor Kidney Transplants

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Treatment of recurrent hepatitis C virus infection in patients after liver transplantation

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