Epithelioid Hemangioendothelioma in a Liver Transplant Recipient: A Case Report of an Extremely Rare Tumor.

Epithelioid hemangioendothelioma is a very rare vascular neoplasm, which is often multifocal or metastatic at diagnosis. Most frequently arises in the liver, followed by the lung and bones. The authors present a case of a liver transplant recipient who developed a pattern of hepatic cholestasis associated with the appearance of a proliferative hepatic lesion with infiltrative growth. Histological examination and immunohistochemical study were compatible with the diagnosis of epithelioid hemangioendothelioma. Pulmonary micronodules were detected and lung metastases were hypothesized. Therefore, bronchoscopy was performed, which turned out to be normal, and cytology was negative for neoplastic cells. After a multidisciplinary discussion, liver re-transplantation was decided. After 8 years of follow-up, the patient is clinically stable, with no graft dysfunction, no neoplastic recurrence, and dimensional stability of the pulmonary micronodules. Patients with organ transplant have higher risk of developing carcinoma compared to the general population. The development of cancer is a multifactorial process and little is known about the etiology of epithelioid hemangioendothelioma. No standard treatment strategy has been defined yet, and the natural course of the disease is heterogenous and the individual prognosis unpredictable. Complete surgical resection is offered to patients with unifocal disease, and those with unresectable disease should be evaluated for orthotopic liver transplantation.

O hemangioendotelioma epitelióide é uma neoplasia vascular extremamente rara, muitas vezes multifocal ou metastática ao diagnóstico. O local mais frequente afetado é o fígado, seguido pelo pulmão e ossos. Os autores apresentam o caso de uma doente com antecedentes de transplante hepático que desenvolveu um padrão de colestase associado ao aparecimento de uma lesão hepática proliferativa e de crescimento infiltrativo. O exame histológico e o estudo imuno-histoquímico foram compatíveis com hemangioendotelioma epitelióide. Foram detetados micronódulos pulmonares, tendo sido colocada a hipótese de se tratarem de metástases pulmonares. Assim, foi realizada broncoscopia, que não revelou alterações, estando a citologia negativa para células neoplásicas. Após discussão multidisciplinar, foi decidido o retransplante hepático. Após 8 anos de seguimento, a doente encontra-se clinicamente estável, sem disfunção do enxerto, sem recidiva neoplásica e com estabilidade dimensional dos micronódulos pulmonares. Doentes submetidos a transplante têm maior risco de desenvolver neoplasias em comparação com a população geral. O desenvolvimento da neoplasia é um processo multifatorial, sendo a etiologia do hemangioendotelioma epitelióide ainda pouco compreendida. Não existe uma estratégia terapêutica standard, sendo o curso natural da doença heterogêneo e o prognóstico individual imprevisível. A ressecção cirúrgica é a primeira opção terapêutica nos doentes com doença unifocal, aqueles com doença irressecável devem ser avaliados para transplante hepático.

Correlation between neuroimaging, neurological phenotype, and functional outcomes in Wilson's disease.

INTRODUCTION: Wilson's disease (WD) is associated with a variety of movement disorders and progressive neurological dysfunction. The aim of this study was to correlate baseline brain magnetic resonance imaging (MRI) features with clinical phenotype and long-term outcomes in chronically treated WD patients. METHODS: Patients were retrospectively selected from an institutional database. Two experienced neuroradiologists reviewed baseline brain MRI. Functional assessment was performed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) scale, and disease severity was classified using the Global Assessment Scale for Wilson's Disease (GASWD). RESULTS: Of 27 patients selected, 14 were female (51.9%), with a mean (standard deviation [SD]) age at onset of 19.5 (7.1) years. Neurological symptoms developed in 22 patients (81.5%), with hyperkinetic symptoms being the most common (70.4%). Baseline brain MRI showed abnormal findings in 18 cases (66.7%), including T2 hyperintensities in 59.3% and atrophy in 29.6%. After a mean (SD) follow-up of 20.9 (11.0) years, WD patients had a mean score of 19.2 (10.2) on WHODAS 2.0 and 6.4 (5.7) on GASWD. The presence of hyperkinetic symptoms correlated with putaminal T2 hyperintensities (p = 0.003), putaminal T2 hypointensities (p = 0.009), and mesencephalic T2 hyperintensities (p = 0.009). Increased functional disability was associated with brain atrophy (p = 0.007), diffusion abnormalities (p = 0.013), and burden of T2 hyperintensities (p = 0.002). A stepwise regression model identified atrophy as a predictor of increased WHODAS 2.0 (p = 0.023) and GASWD (p = 0.007) scores. CONCLUSIONS: Atrophy and, to a lesser extent, deep T2 hyperintensity are associated with functional disability and disease severity in long-term follow-up of WD patients.

Liver Transplantation for Acute Hepatic Failure Following Intentional Iron Overdose.

The majority of acute iron toxicity cases occur in young children from accidental ingestion. In adults, iron poisoning is rare and mostly due to intentional ingestion. Physicians, particularly those who do not routinely treat pediatric patients, are often unfamiliar with the clinical manifestation of iron poisoning, its management, and its potential for multiple organ failure, especially liver damage. Severe acute hepatotoxicity treated with liver transplantation is rare in adults, with very limited published literature. We report a case of a severe iron tablet overdose with suicidal intent that progressed to fulminant hepatic failure despite medical treatment, ultimately treated with liver transplantation.

Trace Element Imbalances in Acquired Hepatocerebral Degeneration and Changes after Liver Transplant.

Brain manganese (Mn) accumulation is a key feature in patients with acquired hepatocerebral degeneration (AHD). The role of trace elements other than Mn in AHD needs to be clarified. In this study, using inductively coupled plasma mass spectrometry, we aimed to evaluate blood levels of trace elements in patients with AHD before and after liver transplantation (LT). Trace element levels in the AHD group were also compared with those of healthy controls (blood donors, n = 51). Fifty-one AHD patients were included in the study (mean age: 59.2 ± 10.6 years; men: 72.5%). AHD patients had higher levels of Mn, Li, B, Ni, As, Sr, Mo, Cd, Sb, Tl and Pb and a higher Cu/Se ratio, and lower levels of Se and Rb. Six patients (two women; mean age 55 ± 8.7 years) underwent LT, and there was an improvement in neurological symptoms, a significant increase in the Zn, Se and Sr levels, and a decrease in the Cu/Zn and Cu/Se ratios. In summary, several trace element imbalances were identified in AHD patients. Liver transplantation resulted in the improvement of neurological manifestations and the oxidant/inflammatory status. It is possible that observed changes in trace element levels may play a role in the pathophysiology and symptomatology of AHD.

Painless rash in a transplant patient.

Dermatophytes are common keratinophilic fungi responsible for superficial skin infections. Deep dermatophytosis is a rare form of invasive skin infection described in immunocompromised patients. We report the case of a 65-year-old man with a history of an orthotopic liver transplant for hepatocarcinoma 6 months earlier, who presented with small painless erythematous papules in lower limbs, some of which were umbilicated. Skin biopsy showed an intense non-necrotizing granulomatous reaction in the dermis around fungal structures. Trichophyton rubrum was identified as the causal agent through culture and internal transcribed spacer sequencing.

Systemic inflammation as a risk factor for portal vein thrombosis in cirrhosis: a prospective longitudinal study.

BACKGROUND AND AIMS: Various risk factors for portal vein thrombosis (PVT) development in patients with cirrhosis have been identified, but the role of systemic inflammatory reaction is unknown. The study aims to assess the association between markers of systemic inflammation and PVT in cirrhosis. METHODS: Between January 2014 and October 2015, 107 outpatients with cirrhosis and no PVT were recruited, and followed till February 2017. White blood cell count, serum concentrations of high-sensitive C-reactive protein, ferritin, tumor necrosis factor-alpha and interleukin-6 (IL-6) were evaluated at baseline and every 3 or 6 months till PVT diagnosis or end of follow-up. RESULTS: Median age, model for end-stage liver disease (MELD) score and follow-up period of the studied population was 55 years (IQR 46-62 years), 9.6 points (IQR 7.5-12 points) and 19 months (12-24 months), respectively. PVT developed in 10.3% of the patients. Lymphocyte count below 1.2 ´ 109/L [hazard ratio, 6.04; 95% confidence interval (CI), 1.29-28.2; P = 0.022], IL-6 above 5.5 pg/mL (hazard ratio, 5.64; 95% CI, 1.21-26.33; P = 0.028) and neutrophil-to-lymphocyte ratio (hazard ratio, 1.46; 95% CI, 1.04-2.04; P = 0.028) were associated with a higher risk of PVT development. IL-6 and lymphopenia remained associated with subsequent PVT development after adjustment for nonselective beta-blockers, spleen size, portosystemic collaterals, oesophageal varices (grade ≥2) and ascites, but also with alcohol as the cause for cirrhosis and MELD ≥13. CONCLUSION: In patients with cirrhosis, markers of systemic inflammation IL-6 and lymphopenia are predictive of PVT independently of markers of portal hypertension. These results draw our attention on a factor so far overlooked in the pathogenesis of PVT.

Nonselective beta-blockers and the risk of portal vein thrombosis in patients with cirrhosis: results of a prospective longitudinal study.

BACKGROUND: Nonmalignant portal vein thrombosis is a significant event in the course of cirrhosis that can contraindicate liver transplantation and even impact survival after the surgical procedure. Risk factors are not completely known or validated and are still debated. AIM: To identify in patients with cirrhosis the risk factors for portal vein thrombosis that are assessable in clinical practice. METHODS: Between January 2014 and February 2017, 108 outpatients with cirrhosis and no portal vein thrombosis (78% Child A) were enrolled. Doppler ultrasound was performed every 3 or 6 months, for a median follow up of 19 months. RESULTS: Portal vein thrombosis developed in 11 patients. Nonselective beta-blockade (hazard ratio [HR] 10.56; 95% confidence interval [CI]: 1.35-82.73; P = 0.025), and medium or large-sized oesophageal varices (HR 5.67; 95% CI: 1.49-21.63; P = 0.011) at baseline were associated with portal vein thrombosis development. Although heart rate (P < 0.001) and portal blood flow velocity at baseline (P = 0.005) were significantly reduced by nonselective beta-blockers, they were not related to portal vein thrombosis development. CONCLUSIONS: Our findings confirm an association between portal vein thrombosis development and oesophageal varices at baseline, but suggest that the association could be explained by exposure to nonselective beta-blockers, independently from effects on heart rate and portal blood flow velocity. The mechanisms that explain portal vein thrombosis development in patients on nonselective beta-blockers require elucidation in order to optimise targeting of nonselective beta-blockade in patients with cirrhosis.

Post liver transplant tuberculosis.

We report on a patient diagnosed with disseminated (hepatic and pulmonary) tuberculosis in the context of immunosuppression following liver transplant. During the administration of anti-tuberculosis drugs an abrupt elevation of liver enzymes was detected leading us to suspect drug toxicity rather than graft rejection. Nevertheless, careful surveillance and adjustment of serum levels of immunosuppressant drugs permitted continuance of tuberculosis treatment with no further side effects.