Julien Vionnet

HIV-Positive-to-HIV-Positive Liver Transplantation.

Most countries exclude human immunodeficiency virus (HIV)‐positive patients from organ donation because of concerns regarding donor‐derived HIV transmission. The Swiss Federal Act on Transplantation has allowed organ transplantation between HIV‐positive donors and recipients since 2007. We report the successful liver transplantation from an HIV‐positive donor to an HIV‐positive recipient. Both donor and recipient had been treated for many years with antiretroviral therapy and harbored multidrug‐resistant viruses. Five months after transplantation, HIV viremia remains undetectable. This observation supports the inclusion of appropriate HIV‐positive donors for transplants specifically allocated to HIV‐positive recipients.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus.

This study was undertaken to investigate how aging affects dermal microvascular reactivity in skin areas differentially exposed to sunlight, and therefore to different degrees of photoaging.

Tocilizumab for giant cell arteritis with corticosteroid-resistant progressive anterior ischemic optic neuropathy

BACKGROUND Giant cell arteritis is an inflammatory disorder of the medium- and large-size arteries. Permanent visual loss related to arteritic anterior ischemic optic neuropathy is among the most serious complications of this disease and initial treatment usually consists of high dose corticosteroids. There is no consensus in the literature concerning the optimal therapeutic approach in giant cell arteritis patients with corticosteroid-resistant arteritic anterior ischemic optic neuropathy. CASE REPORT A 73-year-old Caucasian female with biopsy-proven giant cell arteritis developed an acute visual loss of the right eye due to arteritic anterior ischemic optic neuropathy. Despite 5 daily methylprednisolone pulses, systemic symptoms persisted and rapid involvement of the controlateral eye was documented. Therefore, tocilizumab (humanised monoclonal antibody binding the human interleukin-6 receptor) was introduced as a potential salvage therapy with a swift consecutive resolution of the systemic symptoms and stabilization of the ophthalmic lesions. CONCLUSIONS Although a late effect of steroids pulses cannot be formally ruled out in this dramatic situation, tocilizumab likely offered a decisive effect in preventing bilateral blindness and may have contributed to steroid tapering. Tocilizumab may represent a new early effective second-line treatment option in corticosteroid-resistant anterior ischemic optic neuropathy. More data are needed to confirm this observation and to evaluate the safety profile of this treatment.

Biomarkers of immune tolerance in liver transplantation

The liver exhibits intrinsic immune tolerogenic properties that contribute to a unique propensity toward spontaneous acceptance when transplanted, both in animal models and in humans. Thus, in contrast to what happens after transplantation of other solid organs, several years following liver transplantation a significant subset of patients are capable of maintaining normal allograft function with histological integrity in the absence of immunosuppressive drug treatment. Significant efforts have been put into identifying sensitive and specific biomarkers of tolerance in order to stratify liver transplant recipients according to their need for immunosuppressive medication and their likelihood of being able to completely discontinue it. These biomarkers are currently being validated in prospective clinical trials of immunosuppression withdrawal both in Europe and in the United States. These studies have the potential to transform the clinical management of liver transplant recipients by mitigating, at least in part, the burden of lifelong immunosuppression.

Late hepatitis B reactivation following direct‐acting antiviral–based treatment of recurrent hepatitis C in an anti‐HBc–positive liver transplant recipient

Direct‐acting antivirals (DAAs) have changed the landscape of hepatitis C virus (HCV) treatment, but chronic hepatitis C (CHC) remains a leading indication for liver transplantation (LT). Hepatitis B virus (HBV) reactivation has been reported in HBV‐HCV‐coinfected patients treated with DAAs. We report on a case of late HBV reactivation after DAA‐based treatment of recurrent hepatitis C in an antibody against hepatitis B core antigen (anti‐HBc)‐positive LT recipient. (Hepatology 2018;67:791‐793).

Late hepatitis B reactivation following DAA-based treatment of recurrent hepatitis C in an anti-HBc-positive liver transplant recipient

Direct‐acting antivirals (DAAs) have changed the landscape of hepatitis C virus (HCV) treatment, but chronic hepatitis C (CHC) remains a leading indication for liver transplantation (LT). Hepatitis B virus (HBV) reactivation has been reported in HBV‐HCV‐coinfected patients treated with DAAs. We report on a case of late HBV reactivation after DAA‐based treatment of recurrent hepatitis C in an antibody against hepatitis B core antigen (anti‐HBc)‐positive LT recipient. (Hepatology 2018;67:791‐793).

Eculizumab and Intravenous Immunoglobulins for the Treatment of Acute Antibody-Mediated Rejection after Lung and Liver Transplantation

Introduction Acute antibody-mediated rejection (aAMR) management remains challenging. We report 2 cases of aAMR treated with a single dose of eculizumab (ECZ) 600 mg, followed by 3 weekly high-dose intravenous immunoglobulins (IVIG) 2 g/kg (“ECZ-IVIG”), in a lung and a liver recipients. One single dose of rituximab (RTX) was administered to the lung recipient, however the liver recipient refused it. Case 1 A 48-year-old female received a bilateral lung transplantation (Tx) because of lymphangioleiomyomatosis. A preformed class II (anti-DR17 mean fluorescence intensity [MFI] 1783) donor-specific antibody (DSA) was detectable prior to Tx, but flow cytometry T and B crossmatches were negative. The patient developed rapidly progressive dyspnea and hypoxemia at post-operative day (POD) 7, with new pulmonary infiltrates. A repeat Luminex® assay on POD9 revealed class I (anti-A24 MFI 3978, anti-B8 MFI 1886) and class II (anti-DR17 MFI 19088, anti-DQ2 MFI 3440) DSA, along with de novo positive flow cytometry crossmatches. Lung biopsy showed C4d deposits in the pulmonary capillaries but without acute cellular rejection. The ECZ-IVIG treatment was administered, followed by one infusion of RTX 375 mg/m2 at POD28. Hypoxemia strikingly improved after ECZ administration and oxygenotherapy could be stopped at POD14. DSA progressively decreased (MFI<2000 by POD41) and remained at low-titers thereafter. The patient is well more than 3 years post-Tx. Case 2 A 52-year-old female, who had received 4 years earlier a liver Tx for toxic acute liver failure, stopped her immunosuppression without medical advice. One month later, abnormal liver function tests (AST 236 U/l, ALT 286 U/l, alkaline phosphatase 420 U/l, &ggr;-GT 310 U/l, total bilirubin 85 &mgr;mol/l), along with high-titers de novo DSA (anti-DQ2 MFI 19576 and anti-DR7 MFI 2368), were detected. Liver biopsy showed severe acute rejection (rejection activity index 7/9) with diffuse endothelitis, destructive ductulitis (ductopenia <50%) and moderate fibrosis (F2), without endothelial C4d deposits. The ECZ-IVIG treatment was administered, along with 500 mg/d iv methylprednisolone for 4 days, with a progressive normalization of liver function tests and decrease in DSA titers. A liver biopsy one month after this combined treatment showed disappearance of the acute rejection and stabilization of the biliary lesions and ductopenia. Discussion ECZ administration was associated in both cases with a rapid improvement in lung and liver allograft function, likely highlighting the humoral mechanistic process of rejection involving DSA and complement activation. Because ECZ does not suppress DSA production, ECZ was followed by IVIG administration. No thymoglobulin treatment was necessary. Conclusion The ECZ-IVIG treatment was safe and associated with clinical, immunological and histological improvement in both recipients diagnosed with aAMR. This regimen should be further prospectively studied in the setting of aAMR after lung and liver Tx.

Sofosbuvir and ribavirin before liver re-transplantation for graft failure due to recurrent hepatitis C: a case report

BackgroundRecurrent hepatitis C virus infection after liver transplantation is associated with reduced graft and patient survival. Re-transplantation for graft failure due to recurrent hepatitis C is controversial and not performed in all centers.Case presentationWe describe a 54-year-old patient with hepatitis C virus genotype 1b infection and a null response to pegylated interferon-α and ribavirin who developed decompensated graft cirrhosis 6 years after a first liver transplantation. Treatment with sofosbuvir and ribavirin allowed for rapid negativation of serum HCV RNA and was well tolerated despite advanced liver and moderate renal dysfunction. Therapeutic drug monitoring did not reveal any clinically significant drug-drug interactions. Despite virological response, the patient remained severely decompensated and re-transplantation was performed after 46 days of undetectable serum HCV RNA. The patient is doing well 12 months after his second liver transplantation and remains free of hepatitis C virus.ConclusionsThe use of directly acting antivirals may allow for successful liver re-transplantation for recipients who remain decompensated despite virological response and is likely to improve the outcome of liver re-transplantation for end-stage recurrent hepatitis C.