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Lookup NU author(s): Professor Andrew GenneryORCiD
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The autoimmune lymphoproliferative syndrome (ALPS) is a rare, multisystemic disease, caused by an inherited defect in the Fas apoptotic pathway, characterized by a chronic non-malignant lymphoid accumulation and autoimmune manifestations. Lung, kidney, liver, and gut infiltration is described in severe, multisystemic cases; so far there has been no description of hepatopulmonary syndrome (HPS), for which orthotopic liver transplantation (OLT) is currently the only known effective treatment. A teenage boy, diagnosed with ALPS at 4years of age (lymph nodes enlargement, splenomegaly, immune cytopenias), was stable until 13years of age, when he developed insidious hypoxemia (PaO2=46.7mmHg). He was diagnosed with HPS on the basis of hypoxemia, non-cirrhotic liver disease with portal hypertension, and pulmonary vascular dilatation (intrapulmonary shunt=45%). He was treated with oxygen (maximum 6L/min), prednisolone and sirolimus. There was significant regression of all manifestations of ALPS, except for the pulmonary symptoms, therefore, after evaluation in referral centers in England, OLT was proposed. Since he was to undergo major surgery, sirolimus, which has wound-healing problems, was switched to mycophenolate mofetil (MMF). Following this change, we observed a huge improvement in pulmonary symptoms and reduction of oxygen needs. The intrapulmonary shunt decreased from 45% to 0% in less than a year, and it has not changed since (18months after complete normalization), on continued treatment with MMF. Indication for OLT was suspended. In the last year, lymphoid proliferation increased again, with huge splenomegaly, but no recurrence of HPS. The addition of sirolimus to MMF produced again a rapid resolution of lymphoid proliferation. The dramatic and unexpected regression of HPS may have been due to inhibition of angiogenesis and nitric oxide (NO) production by MMF (both important pathways/mediators in HPS pathogenesis). Therefore, we propose to perform clinical trials with MMF, and/or other angiogenesis and NO inhibitors, on a long-term treatment basis, to confirm their potential as a valid alternative to medical treatment of HPS.
Author(s): Silva HM, Reis G, Guedes M, Cleto E, Vizcaino JR, Kelly D, Gennery AR, Silva ES
Publication type: Article
Publication status: Published
Journal: Journal of Hepatology
Year: 2013
Volume: 58
Issue: 3
Pages: 630-633
Print publication date: 01/03/2013
ISSN (print): 0168-8278
ISSN (electronic): 1600-0641
Publisher: Elsevier
URL: http://dx.doi.org/10.1016/j.jhep.2012.10.021
DOI: 10.1016/j.jhep.2012.10.021
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