Developmental Disorders of the Lymphatics

An information blog for disorders of the lymphatics. For all articles, please click on "Archives" - Due to spammers, I will no longer allow comments, sorry.

Monday, November 19, 2012

A Case of Hepatopulmonary Syndrome Solved by Mycophenolate Mofetil (An Inhibitor Of Angiogenesis and Nitric Oxid Production).

A Case of Hepatopulmonary Syndrome Solved by Mycophenolate Mofetil (An Inhibitor Of Angiogenesis and Nitric Oxid Production).

Oct 2012


Pediatric Gastroenterology Unit, Department of Child and Adolescent, Centro Hospitalar do Porto, Portugal.



The autoimmune lymphoproliferative syndrome (ALPS) is a rare, multi-systemic disease, caused by an inherited defect in the Fas apoptotic pathway, characterized by a chronic non-malignant lymphoid accumulation, andautoimmune manifestations. Lung, kidney, liver, and gut infiltration is described in severe, multi-systemic cases; so far there is 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 4 years old (lymph nodes enlargement, splenomegaly, immune cytopenias), was stable until 13 years old when he developed insidiously hypoxemia (PaO2 = 46.7 mmHg). He was diagnosed with HPS on the basis of hypoxemia, non-cirrhotic liver disease with portal hypertension, and pulmonary vascular dilatation (intra-pulmonary shunt = 45%). He was treated with oxygen (maximum 6 liters/minute), prednisolone and sirolimus. There was significant regression of all manifestations of ALPS, except the pulmonary symptoms, so, after evaluation in referral centers in England, OLT was proposed. Since he was to be submitted to major surgery, sirolimus, which has wound healing problems, was switched for mycophenolate mofetil (MMF). Following this change, we observed an enormous improvement of the pulmonary symptoms and reduction of oxygen needs. The intra-pulmonary shunt decreased from 45% to 0% in less than a year, and remains so until today (18 months 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 the HPS pathogenesis). Therefore, we propose the conduct of clinical trials with MMF, and/or other angiogenesis and NO inhibitors, in a long-term treatment basis, to confirm their potential as a valid alternative for medical treatment of HPS.

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