Palliative Care in Advanced Liver Disease: Similar or Different Palliative Care Needs in Patients with a Prospect of Transplantation? Prospective Study from a Portuguese University Hospital and Transplantation Center.

Background and Aims: End-stage liver disease (ESLD) is an important cause of morbidity and mortality, comparable to a large extent to other organ insufficiencies. The need for palliative care (PC) in patients with ESLD is high. In Portugal, in the only identified study, more than 80% of patients hospitalized with ESLD had criteria for PC. No results specified which needs they identified or their transplantation prospect status. Methods: Prospective observational study including 54 ESLD patients who presented to a university hospital and transplantation center, between November 2019 and September 2020. Assessment of their PC needs through the application of NECPAL CCOMS-ICO© and IPOS, considering their transplantation perspective status. Results: Of the 54 patients, 5 (9.3%) were on active waiting list for transplantation and 8 (14.8%) under evaluation. NECPAL CCOMS-ICO© identified 23 patients (n = 42.6%) that would benefit from PC. Assessment of PC needs by clinicians, functional markers and significant comorbidities were the most frequent criteria (47.8%, n = 11). IPOS also revealed a different sort of needs: on average, each patient identified about 9 needs (8.9 ±2.8). Among the symptoms identified, weakness (77.8%), reduced mobility (70.3%), and pain (48.1%) stood out, as well as the psychoemotional symptoms of depression (66.7%) and anxiety (77.8%). There were no significant differences between the subgroups of patients analyzed. Only 4 patients (7.4%) were followed by the PC team. Conclusion: All the ESLD patients included, independently of the group they belonged to, presented with PC needs. No significant differences between the subgroups of patients were identified, confirming that even patients with a transplantation prospect have important needs for PC.

Introdução e objetivos: A doença hepática avançada (DHA) é uma causa importante de morbilidade e mortalidade, comparável em grande medida a outras insuficiências de órgão. A necessidade de cuidados paliativos (CP) em doentes com DHA é elevada. Em Portugal, no único estudo identificado até ao momento, mais de 80% dos doentes hospitalizados com DHA apresentavam critérios para CP. Não foram especificadas que necessidades de CP nem a perspetiva de transplante dos referidos doentes, que com o presente estudo se pretende ajudar a esclarecer. Métodos: Estudo prospectivo observacional incluindo 54 doentes com DHA assistidos num hospital universitário e centro de transplante, entre novembro de 2019 e setembro de 2020. Avaliação das necessidades de CP por meio da aplicação do NECPAL CCOMS-ICO© e IPOS, considerando a sua perspectiva de transplante. Resultados: Dos 54 doentes, cinco (9,3%) estavam em lista de espera ativa para transplante e oito (14,8%) em avaliação. O NECPAL CCOMS-ICO© identificou 23 doentes (n = 42,6%) que beneficiariam de CP. A avaliação das necessidades de CP por médicos, os marcadores funcionais e as comorbidades significativas foram os critérios mais frequentes (47,8%, n = 11). O IPOS também revelou diversas necessidades de CP: em média, cada doente identificou cerca de 9 necessidades (8,9 + −2,8). Entre os sintomas identificados, destacaram-se a fraqueza (77,8%), a mobilidade reduzida (70,3%) e a dor (48,1%), bem como os sintomas psicoemocionais de depressão (66,7%) e ansiedade (77,8%). Não houve diferenças significativas entre os subgrupos de doentes analisados. Apenas 4 doentes (7,4%) foram acompanhados pela equipa intra-hospitalar de CP. Conclusão: Todos os doentes com DHA incluídos, independentemente do grupo a que pertenciam, apresentaram necessidades de CP. Não foram identificadas diferenças significativas entre os subgrupos de doentes, confirmando que mesmo os doentes com perspectiva de transplante têm importantes necessidades de CP.

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.

Palliative Care in End-Stage Liver Disease Patients Awaiting Liver Transplantation: Review.

INTRODUCTION: End-stage liver disease (ESLD) is the advanced phase of most liver diseases. The cure is liver transplantation (LT), only available for a minority of patients. This review summarizes the evidence regarding palliative care (PC) in ESLD patients awaiting LT. METHODS: Review of the literature available in Medline, Scopus and Web of Knowledge, with keywords ESLD and PC. RESULTS: Fifteen of the 230 articles reviewed met the inclusion criteria. Ten main themes were addressed: symptom burden; perspectives of life-sustaining treatment and comfort for patients, families and health professionals; goals of care discussions; patient and family needs; quality of life; PC and survival; referral to PC, barriers and opportunities; integration of PC; outpatient care and cost-effectiveness analysis. The referral of patients to PC was only evaluated in a few studies, all of which reported low referral rates. Better knowledge of how PC professionals can support other professionals was considered important, and also better ways to integrate PC were considered essential. CONCLUSION: ESLD patients awaiting LT have a significant need for PC and, despite the insufficient response, were reported to benefit from this type of care. Future research is essential to determine the means to overcome barriers and better integrate PC for ESLD patients awaiting LT.

INTRODUÇÃO: A doença hepática avançada (DHA) corresponde à fase mais avançada das doenças hepáticas. O transplante hepático (TH) é o tratamento curativo, disponível apenas para uma minoria de doentes. Esta revisão sumariza a evidência sobre cuidados paliativos (CP) em doentes com DHA que aguardam TH. MÉTODOS: Revisão da literatura existente na Medline, Scopus e Web of Knowledge. Palavras chave pesquisadas CP e DHA. RESULTADOS: Quinze dos 230 artigos encontrados cumpriram critérios de inclusão. Dez temáticas foram abordadas: carga sintomática; discussão de objectivos de cuidados; perspectivas sobre tratamentos de suporte artificial e conforto; necessidades do doente e família; qualidade de vida; CP e impacto no prognóstico; referenciação para CP, barreiras e oportunidades; integração dos CP; cuidados de ambulatório e análises de custo-benefício. Poucos estudos avaliaram a referenciação para CP, todos com baixas taxas. Mais conhecimento e formação dos profissionais que acompanham doentes com DHA parece ser necessário, bem como, melhor articulação entre os diferentes intervenientes. CONCLUSÃO: Doentes com DHA que aguardam TH apresentam importantes necessidades de CP. Apesar da insuficiente resposta a este nível, parecem beneficiar deste tipo de cuidados. Estudos futuros que clarifiquem como ultrapassar as barreiras e a melhor integração dos CP nos doentes que aguardam TH são essenciais.

Accurate simultaneous quantification of liver steatosis and iron overload in diffuse liver diseases with MRI.

PURPOSE: To evaluate the diagnostic performances of 3 Tesla multi-echo chemical shift-encoded gradient echo magnetic resonance (MECSE-MR) imaging to simultaneously quantify liver steatosis and iron overload in a wide spectrum of diffuse liver diseases having biopsy as reference standard. METHODS: MECSE-MR-acquired images were used to calculate fat fraction and iron content in a single breath-hold in 109 adult patients. Proton density fat fraction (PDFF) was prospectively estimated using complex-based data reconstruction with multipeak fat modeling. Water R2* was used to estimate iron content. Biopsy was obtained in all cases, grading liver steatosis, siderosis, inflammation, and fibrosis. Differences in PDFF and R2* values across histopathological grades were analyzed, and ROC curves analyses evaluated the MR diagnostic performance. RESULTS: Calculated fat fraction measurements showed significant differences (p < 0.001) among steatosis grades, being unaffected by the presence of inflammation or fibrosis (p ≥ 0.05). A strong correlation was found between fat fraction and steatosis grade (R S = 0.718, p < 0.001). Iron deposits did not affect fat fraction quantitation (p ≥ 0.05), except in cases with severe iron overload (grade 4). A strong positive correlation was also observed between R2* measurements and iron grades (R S = 0.704, p < 0.001). Calculated R2* values were not different across grades of steatosis, inflammation, and fibrosis (p ≥ 0.05). CONCLUSION: A MECSE-MR sequence simultaneously quantifies liver steatosis and siderosis, regardless coexisting liver inflammation or fibrosis, with high accuracy in a wide spectrum of diffuse liver disorders. This sequence can be acquired within a single breath-hold and can be implemented in the routine MR evaluation of the liver.

A New Mutation Causing Progressive Familiar Intrahepatic Cholestasis Type 3 in Association with Autoimmune Hepatitis.

BACKGROUND: Some patients exhibit features of both autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). Similarly, patients with progressive familial intrahepatic cholestasis type 3 (PFIC3) may share histological features with PSC. CASE REPORT: We report the case of a 22-year-old man who, since he was 5 years of age, has presented with pruritus, an approximately ninefold elevation of aminotransferases, and γ-glutamyl transferase levels ~10 times the upper limit. Initially he was diagnosed with an overlap syndrome of small duct PSC plus AIH. However, fluctuations in liver enzymes were observed over the following years. Analysis of the ABCB4 gene indicated the diagnosis of PFIC3, revealing a mutation not previously reported. CONCLUSION: With this case report we aim to describe a new mutation, raise awareness of this rare pathology and highlight the importance of genetic testing of the ABCB4 gene in patients with autoimmune liver disease (mainly small duct PSC) with incomplete response to immunosuppressive treatment. LEARNING POINTS: Autoimmune liver diseases have a wide spectrum of manifestations.Cholangiopathies such as ABCB4 deficiency have histological features quite similar to those seen in small duct primary sclerosing cholangitis.The new mutation of the ABCB4 gene described in this article is compatible with the diagnosis of progressive familial intrahepatic cholestasis type 3, which is probably less rare than usually thought.

Elevation of gamma-glutamyl transferase in adult: Should we think about progressive familiar intrahepatic cholestasis?

BACKGROUND: There are three types of progressive familial intrahepatic cholestasis (PFIC). Type 3 is characterized by elevated gamma-glutamyl transferase (γ-GT) and it can be diagnosed in adolescence/adulthood. The genetic defect of PFIC 3 appears to explain the pathogenesis of intrahepatic cholestasis of pregnancy (ICP). AIMS: Draw attention to this rare disease, especially in adulthood, and clarify the association between ICP and PFIC 3. RESULTS: We describe a series of cases from a Portuguese northern family with two brothers presenting chronic cholestasis since adolescence. Brother 1: since 15-years-old with pruritus and elevated γ-GT ∼6x. Brother 2: pre-term, due to severe maternal pruritus and jaundice, since 13-years-old with pruritus, jaundice and ∼8x γ-GT elevation. Common causes of cholestasis were excluded and liver histologies were nonspecific. Research for mutation on ABCB4 gene showed mutations in both alleles. CONCLUSION: Disease and mechanisms that determine cholestasis are complex and their understanding may provide new therapeutics.