Longterm use of a calcineurin inhibitor (CNI)–based regimen is one of the major reasons for chronic renal failure in liver transplantation recipients (LTRs). The Everolimus Liver registry ...(EVEROLIVER) evaluated renal function in LTRs who were converted to everolimus (EVR). This observational registry included all LTRs receiving EVR across 9 centers from France. Data are being collected in an electronic database over 10 years (12 visits/patient) to evaluate efficacy, renal function (estimated glomerular filtration rate eGFR), and safety of EVR use in clinical practice, and the current analysis is reporting up to 60 months of findings. Until September 2017, 1045 patients received EVR after a mean time of 3.6 ± 5.1 years. CNI withdrawal was feasible in 57.7% of patients as of month 60. Mean eGFR improved in patients with baseline eGFR <60 mL/minute/1.73 m2 and was maintained in those with baseline eGFR ≥60 mL/minute/1.73 m2. Among patients with chronic kidney disease (CKD; baseline eGFR <60 mL/minute/1.73 m2), 55% converted to EVR within 3 months (early conversion) and 39.4% converted between 4 and 12 months after transplantation (mid‐conversion) experienced improvement in eGFR (≥60 mL/minute/1.73 m2) at month 36. Only 20.9% and 17.4% among those converted beyond 12 months (late conversion) experienced improvement respectively at month 36 and 60. A logistic regression analysis in patients with CKD stage ≥3 demonstrated that late conversion, age, and female sex were associated with nonimprovement of eGFR (≥60 mL/minute/1.73 m2). Data from this real‐life use of EVR indicate that renal function was maintained from the preconversion period until month 36 even in patients with advanced CKD. However, early rather than late conversion appears to be a safe approach to preserve longterm renal function in LTRs.
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Summary Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease that necessitates liver transplantation. The incidence of virus-induced cirrhosis and hepatocellular carcinoma ...continues to increase, making liver transplantation increasingly common. Infection of the engrafted liver is universal and accelerates progression to advanced liver disease, with 20–30% of patients having cirrhosis within 5 years of transplantation. Treatments of chronic HCV infection have improved dramatically, albeit with remaining challenges of failure and access, and therapeutic options to prevent graft infection during liver transplantation are emerging. Developments in directed use of new direct-acting antiviral agents (DAAs) to eliminate circulating HCV before or after transplantation in the past 5 years provide renewed hope for prevention and treatment of liver graft infection. Identification of the ideal regimen and use of DAAs reveals new ways to treat this specific population of patients. Complementing DAAs, viral entry inhibitors have been shown to prevent liver graft infection in animal models and delay graft infection in clinical trials, which shows their potential for use concomitant to transplantation. We review the challenges and pathology associated with HCV liver graft infection, highlight current and future strategies of DAA treatment timing, and discuss the potential role of entry inhibitors that might be used synergistically with DAAs to prevent or treat graft infection.
In this article, we describe the case of a 34-year-old woman presenting a multifocal and metastatic epithelioid hemangioendothelioma (HEHE) of the liver. Under classical chemotherapy using ...cyclophosphamide, there was a fast tumor progression in liver and extra-hepatic metastatic sites (lungs and mediastinal lymph node). Taking into account the patient’s age and the natural history of the HEHE, our goal was to try to bring her to liver transplantation (LT) and lenvatinib was an acceptable candidate for this reason. Shortly after the initiation of lenvatinib before LT and surgery, we observed the enlargement of large devascularized necrotic areas in most of the liver HEHE masses, suggesting a good response. The patient was finally transplanted 6 months after initiation of lenvatinib treatment. Eight months after LT, progression occurred (ascites, peritoneal recurrence, and mediastinal lymph node). After restarting lenvatinib, ascites disappeared and the lymph node decreased in size, suggesting a good response, more than 1 year after her transplantation. This is the first case report to our knowledge that illustrates the benefit of lenvatinib as a neoadjuvant bridge until LT for a multifocal and metastatic HEHE. In addition, this drug has also shown a benefit in term of disease control after a late recurrence of the tumor. We suggest that lenvatinib should be proposed as a bridge to the LT for nonresectable HEHE. Moreover, this drug was also beneficial in the treatment of late recurrence after LT. The absence of pharmacologic interactions between classical immunosuppressive drugs and lenvatinib may allow its use as an early adjuvant approach when the risk of recurrence is high. The strength of our case consists in the long follow-up and the innovative message allowing changing palliative strategies into curative ones in case of advanced HEHE.
Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) occurs in 10%–20% of patients transplanted for HCC. The treatment of HCC recurrence after LT remains a challenge. ...Consecutive patients who underwent LT for HCC between 2005 and 2015 at our center were recruited. Characteristics of patients with recurrence, modalities of treatment and outcome were collected retrospectively. Patient survival was analyzed according to HCC recurrence therapeutic strategy. Among 306 transplanted patients, 43 patients (14.1%) developed recurrence with a median survival time after recurrence of 10.9 months (95%CI: 6.6−18.6). Survival of patients treated with Sorafenib (SOR) and everolimus (EVL) (n = 19) was significantly better than that of the group treated with other strategies (n = 24) (P = 0.001). Multivariable analysis demonstrated that SOR plus EVL therapy and absence of dissemination at diagnosis of recurrence were independent predictive factors of prolonged survival after recurrence. Among the patients who treated with EVL, survival of patients with controlled EVL blood trough levels ≥5 ng/ml was significantly better compared to those with EVL trough levels <5 ng/ml (P = 0.021). Combination therapy of sorafenib and everolimus was an independent predictor for better survival after HCC recurrence. Patients with controlled everolimus trough level ≥5 ng/ml might get the best survival benefit.
Liver transplantation is widely used to treat HIV patients with an end-stage liver disease, mainly decompensated cirrhosis and hepatocellular carcinoma. The results are good especially in ...non-hepatitis C virus (HCV)-coinfected patients. In HIV-HCV-coinfected patients, 5-year post-liver transplantation survival is around 50-55%, negatively impacted by HCV recurrence. The results of PEG-IFN/RBV are poor in terms of efficacy and safety. In patients with genotype 1 infection, triple therapy (boceprevir or telaprevir) has increased sustained virological response (SVR) rate, but drug-drug interactions (DDIs) with immunosuppressive agents and high rates of adverse events lead to forsake these combinations. Herein, we provide new data and practical management regarding HIV-HCV liver transplantation patients using new direct-acting antiviral agents (DAA).
The second-generation DAA have good safety profile. In patients who are candidates for liver transplantation or are already recipients, the optimal therapeutic option is to combine the new DAA. Efficacy results have dramatically improved with greater than 90% of SVR rate in many studies enrolling HCV-monoinfected liver transplant recipients. Some concerns persist in terms of DDI.
Even sparse, data regarding efficacy and safety of these regimens in HCV-HIV-coinfected liver transplantation will radically change the prognosis of this peculiar population.
Summary Should organs from hepatitis C antibody positive donors (HCVD+) be used for transplantation? Organ shortage forces transplant teams to use donors with extended criteria. The decision to ...transplant a HCVD+ graft is a balance between the risk of transmission of a virus that could lead to end-stage liver diseases and the benefit of access to transplantation, specifically in patients with life-threatening disease. The other issue is the impact of HCV-related liver fibrosis in the donor graft on the long-term outcome in the recipient. Thus, the use of HCVD+ demonstrated a shorter meantime on the waiting list in kidney transplantation. When a HCVD+ graft is transplanted, the risk of HCV transmission depends on; 1) the quality of screening of the donor; 2) the presence of viral replication in the donor at the time of transplantation and the ability to detect it; and 3) the HCV status of the recipient but also the type of transplanted organ. In liver transplantation, the use of HCVD+ graft is usually restricted to recipients with a chronic HCV infection. Several reports showed some competition between HCV donor and recipient strain without deleterious impact on graft and patient survival. Controversies are still pending regarding the quality of the graft and the progression of fibrosis. The recent approval of direct-acting antiviral agents (DAA) dramatically changes the landscape of HCV infection treatment. After transplantation, combinations of DAA show high efficacy and good safety profile. In the near future, extensive use of DAA should reduce the number of HCVD+ with a positive HCV RNA, limiting the risk of transmission but also the number of patients on waiting lists for a disease related to HCV.
Inherited chromosomally integrated (ici) human herpes virus 6 (HHV-6) is estimated to occur in 0.6-2.7% of people worldwide. HHV-6 comprises two distinct species: HHV-6A and HHV-6B. Both HHV-6A and ...HHV-6B integration have been reported. Several drugs are capable of activating iciHHV-6 in tissues, the consequences of which are poorly understood. We report herein a case of a woman with iciHHV-6A+ and iciHHV-6B+, who developed ulipristal acetate (a selective progesterone receptor modulator)-induced fulminant hepatic failure that required liver transplantation. We confirmed the presence of ~one copy per cell of both HHV-6A and HHV-6B DNA in her hair follicles using multiplex HHV-6A/B real-time PCR and demonstrated the Mendelian inheritance of both iciHHV-6A and iciHHV-6B in her family members over three generations. Because of the rarity of this presentation, we discuss herein the possible links between reactivated HHV-6 from iciHHV-6A and/or iciHHV-6B and adverse drug reactions, suggesting that iciHHV-6 could be screened before the introduction of any hepatotoxic drugs to exclude HHV-6 active disease or combined idiosyncratic drug-induced liver injury in these patients.
Hepatitis C virus (HCV) infection is one of the main causes of end‐stage liver disease and indications for liver transplantation (LT) worldwide. HCV infection always recurs on the graft in patients ...who undergo LT with detectable serum HCV RNA, leading to cirrhosis in 20–30% within 5 years after transplantation. Achieving a sustained virological response (SVR) greatly improves patient and graft survival. Recently, the efficacy of therapy has radically changed and improved based on new direct acting antiviral agents (DAAs) without pegylated‐interferon (PEG‐IFN) and/or ribavirin (RBV), leading to SVR rates of more than 90% in transplanted patients. The safety profile in this population is also good, with limited drug–drug interactions. However, there are very few data on patients on the waiting list. Even when the results of combined DAAs are good (>80%), SVR rates are lower than in patients without cirrhosis. This review reports recent available data on the treatment of HCV infection in the transplant setting and discusses new dilemmas and challenges.
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