Treatment with adalimumab in a patient with regenerative nodular hyperplasia secondary to azathioprine.

INTRODUCTION: regenerative nodular hyperplasia (RNH) is a rare liver disease with an etiology that is not well understood. Among the etiological factors are purine-analogue drugs such asazathioprine. CASE REPORT: we present a case of a 47-year-old patient diagnosed with Crohn´s disease in treatment with azathioprine due to corticosteroid dependency who developed RNH with clinical and laboratory signs of portal hypertension one year after starting treatment. After discontinuation of azathioprine, the patient started treatment and, given the poor disease progression, started treatment with adalimumab. This was continued with an excellent response and without deleterious effects on the liver. DISCUSSION: the relevance of this case is twofold: First, this is a rare and early side effect of azathioprine treatment and this is an irreversible disease with potentially serious complications. Second, because treatment was carried out with biological drugs (adalimumab) despite the patient having advance liver disease with portal hypertension without any evidence of it worsening, nor signs of deleterious effects or complications, given that there is scarce or no experience with adalimumab treatment in this type of situation.

Successful use of ursodeoxycholic acid in nodular regenerative hyperplasia of the liver.

OBJECTIVE: To report, to our knowledge, the first case of a patient with nodular regenerative hyperplasia of the liver (NRHL) associated with portal hypertension in whom ursodeoxycholic acid (UDCA) therapy had a therapeutic effect on liver enzymes and was associated with nonprogression of portal hypertension. CASE SUMMARY: A symptom-free 13-year-old boy was hospitalized for splenomegaly and thrombocytopenia identified during a routine check-up. Infectious, autoimmune, and neoplastic causes were ruled out. Two years later, laboratory findings revealed high levels of aminotransferases and γ-glutamyltransferase (GGT), thrombocytopenia, and neutropenia. Ultrasound scanning of the abdomen confirmed portal hypertension. Results of liver pathology studies showed diagnostic features of NRHL. Given the biochemical evidence of cholestasis, UDCA was administered, with an initial dosage of 10 mg/kg/day that was progressively increased to 20 mg/kg/day (1800 mg/day). After 5 months of treatment, GGT and then aminotransferase levels normalized and remained within normal limits in the following months. With arbitrary withdrawal of UDCA after 30 months of therapy, a rapid increase in transaminase levels was observed. Prompt reinstitution of UDCA was followed by sustained normalization of liver enzymes. Laboratory and sonographic signs of portal hypertension remained stable and tended to improve during UDCA therapy, as demonstrated by regularization of the mean portal vein flow velocity, reduction of the congestion index, progressive increase of the platelet count, and improvement of the esophagogastroscopy pattern. DISCUSSION: NRHL is a rare disease that is characterized by multiple regenerative nodules in the hepatic parenchyma that may lead to noncirrhotic portal hypertension. No specific treatment is available, and management of patients with a primary form of NRHL consists mainly of treating the complications of portal hypertension. In our patient, UDCA therapy was followed by a prompt reduction and sustained normalization of liver enzyme levels and no progression of portal hypertension throughout the follow-up period. CONCLUSIONS: Since in this patient with primary NRHL, ongoing UDCA administration resulted in improved biochemical and portal hypertension markers, this therapy can be considered in cases of NRHL associated with abnormalities of liver enzymes.

Benign liver masses and lesions in children: 53 cases over 12 years.

BACKGROUND: Primary liver masses in children may require intervention because of symptoms or concern about malignant transformation. OBJECTIVES: To review the management and outcome of benign liver masses in children. METHODS: We conducted a retrospective chart review of children with liver masses referred to our institution during the period 1997-2009. RESULTS: Benign liver masses were identified in 53 children. Sixteen of these children (30%) had hemangioma/infantile hepatic hemangioendothelioma (IHH) and 15 (28%) had focal nodular hyperplasia. The remainder had 6 cysts, 4 hamartomas, 3 nodular regenerative hyperplasia, 2 adenomas, 2 vascular malformations, and one each of polyarteritis nodosa, granuloma, hepatic hematoma, lymphangioma, and infarction. Median age at presentation was 6 years, and 30 (57%) were female. Masses were initially noticed on imaging studies performed for unrelated symptoms in 33 children (62%), laboratory abnormalities consistent with liver disease in 11 (21%), and palpable abdominal masses in 9 (17%). Diagnosis was made based on characteristic radiographic findings in 31 (58%), but histopathological examination was required for the remaining 22 (42%). Of the 53 children, 27 (51%) were under observation while 17 (32%) had masses resected. Medications targeting masses were used in 9 (17%) and liver transplantation was performed in 4 (8%). The only death (2%) occurred in a child with multifocal IHH unresponsive to medical management and prior to liver transplant availability. CONCLUSIONS: IHH and focal nodular hyperplasia were the most common lesions. The majority of benign lesions were found incidentally and diagnosed radiologically. Expectant management was sufficient in most children after diagnosis, although surgical intervention including liver transplant was occasionally necessary.

Lenalidomide-induced regenerative macronodules infarction in a cirrhosis patient.

Hepatic regenerative macronodules observed in hepatic cirrhosis are sensitive to ischemia. Lenalidomide is a thalidomide analog used for the treatment of myelodysplastic syndromes, with pleiotropic activities including induction of apoptosis, inhibition of angiogenesis and broad immunomodulatory effects. It has been approved by the Food and Drug Administration (FDA) in the United States and by the European Medicines Agency (EMEA) in 2007 for the use in combination with dexamethasone in the treatment of relapsed or refractory multiple myeloma. We report a unique observation, which strongly suggests the role of Lenalidomide in hepatic regenerative macronodules infarction.

Nodular regenerative hyperplasia of the liver: a rare differential diagnosis of cholestasis with response to ursodeoxycholic acid.

Nodular regenerative hyperplasia of the liver (NRHL) is an uncommon non-malignant finding typically associated with haematological or auto-immune disease. The main clinical symptom is portal hypertension in the absence of underlying liver cirrhosis. The pathogenesis of NRHL remains unknown. We report a case of NRHL with cholestasis and progression to liver insufficiency without any underlying disease and no association with systemic disease or drug intake. Cholestasis and liver function tests improved significantly during treatment with ursodeoxycholic acid (750 mg per day). Based on this case, it may be concluded that treatment with ursodeoxycholic acid might be beneficial in patients with NRHL and progression to liver insufficiency.

Variación de tamaño de la hiperplasia nodular focal mediante resonancia magnética / Variations in the size of focal nodular hyperplasia on magnetic resonance imaging

Objetivo. Evaluar los cambios en el tamaño de la hiperplasia nodular focal (HNF) mediante seguimiento a largo plazo con resonancia magnética (RM). Material y métodos. Se revisaron 44 HNF de 30 pacientes, estudiadas mediante RM con al menos 2 estudios separados como mínimo 12 meses. Se midió (en mm) el diámetro mayor de la lesión en las imágenes transversales de RM con contraste, calculándose el porcentaje de variación como la diferencia entre el diámetro máximo en el seguimiento respecto al diámetro máximo inicial. Se definió como variación significativa de tamaño un porcentaje de variación superior al 20%. Se analizaron los factores hormonales predisponentes. Resultados. La media del intervalo de tiempo entre las 2 pruebas de imagen fue de 35 ± 2 meses (rango: 12-94). La mayoría de las lesiones (80%) permanecieron estables durante el seguimiento, y solo 9 de las 44 lesiones (20%) mostraron una variación significativa de su diámetro. Siete de ellas (16%) disminuyeron de tamaño y 2 (4%) aumentaron, con variaciones que alcanzaron hasta el doble del tamaño inicial. El cambio de tamaño no se pudo relacionar con el embarazo, la menopausia ni el uso de anticonceptivos orales o corticoides. Conclusión. Los cambios de tamaño de la HNF durante el seguimiento son relativamente frecuentes y no deben disuadir de este diagnóstico. Estas variaciones parecen independientes de los factores hormonales considerados como predisponentes (AU)

Objective: To evaluate the changes in the size of focal nodular hyperplasia (FNH) during long- term magnetic resonance imaging (MRI) follow-up. Material and methods: We reviewed 44 FNHs in 30 patients studied with MRI with at least two MRI studies at least 12 months apart. We measured the largest diameter of the lesion (in mm) in contrast-enhanced axial images and calculated the percentage of variation as the difference between the maximum diameter in the follow-up and the maximum diameter in the initial study. We defined significant variation in size as variation greater than 20%. We also analyzed predisposing hormonal factors. Results: The mean interval between the two imaging studies was 35 ± 2 months (range: 12-94). Most lesions (80%) remained stable during follow-up. Only 9 of the 44 lesions (20%) showed a significant variation in diameter: 7 (16%) decreased in size and 2 (4%) increased, with variations that reached the double of the initial size. The change in size was not related to pregnancy, menopause, or the use of birth control pills or corticoids. Conclusion: Changes in the size of FNHs during follow-up are relatively common and should not lead to a change in the diagnosis. These variations in size seem to be independent of hormonal factors that are considered to predispose (AU)