Diagnostic value of novel hepatic fibrosis markers in assessing cirrhosis in patients with chronic hepatitis C / 中华肝脏病杂志

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.

A preliminary discussion on carnosine dipeptidase 1 as a potential novel biomarker for the diagnostic and prognostic evaluation of hepatocellular carcinoma / 中华肝脏病杂志

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Expert consensus on MRI diagnosis of liver fibrosis in chronic hepatitis B (version 2023) / 中华肝脏病杂志

Chronic hepatitis B is a common chronic inflammatory disease of the liver in China that frequently results in sustained damage to the liver parenchyma, followed by liver fibrosis, and ultimately progresses to unfavorable outcomes such as cirrhosis, liver failure, and liver cancer. Liver fibrosis reversal can be achieved through early and effective intervention. Therefore, timely and accurate assessment of the degree of liver fibrosis is of great clinical significance for the treatment and prognosis assessment of patients with chronic hepatitis B. MRI plays a crucial role in the early assessment and monitoring of the therapeutic efficacy of liver fibrosis in chronic hepatitis B. Currently, there is a lack of uniform consensus on MRI scanning protocols and related diagnostic thresholds for liver fibrosis in chronic hepatitis B, which is not conducive to practical clinical evaluation and application. This expert consensus is based on a full review of relevant domestic and international literature and the formulation of methodologies based on evidence-based medical guidelines and standards to develop recommendations for MRI scanning techniques and the diagnosis of liver fibrosis in chronic hepatitis B, with a view to providing a clear basis for the clinical diagnosis.

Progress in the diagnosis of minimal hepatic encephalopathy / 中华肝脏病杂志

Hepatic encephalopathy (HE) is a common serious complication of liver cirrhosis, with sudden onset, indicating a poor prognosis in patients with chronic liver disease. Minimal hepatic encephalopathy (MHE) is an early stage of HE with no apparent symptoms, but it shows abnormal results in neuropsychological and/or neurophysiological tests. MHE affects patients' quality of life, employability, driving ability, and has a high risk of developing overt hepatic encephalopathy (OHE). This article aims to explore various diagnostic methods, strengthen the routine work of clinicians in diagnosis and treatment, and develop an effective MHE screening protocol.

Tratamiento simplificado para pacientes con Hepatitis C / Simplified treatment for hepatitis C patients

El nuevo tratamiento simplificado con antivirales orales para pacientes con Hepatitis C puede ser abordado desde la atención primaria, lo que facilita el acceso de la población afectada por esta infección crónica. En este artículo se repasan los aspectos claves del diagnóstico, el esquema de tratamiento simplificado y los candidatos a recibirlo. (AU)

The new simplified treatment with oral antivirals for hepatitis C patients can be approached at the primary care level, facilitating access for the population affected by this chronic infection. This article reviews the key aspects of the diagnosis, the simplified treatment scheme, and the eligible candidates for the treatment. (AU)

Estudio descriptivo de pacientes con cirrosis hepática de etiología viral, en la provincia de Matanzas / Descriptive study of patients with viral-etiology liver cirrhosis in the province of Matanzas

RESUMEN Introducción: la cirrosis hepática de etiología viral representa un impactante problema de salud a nivel mundial, no solo por su elevada tasa de prevalencia, sino por los costos generados en la atención médica. Objetivos: determinar el comportamiento de los pacientes cirróticos, de etiología viral, en la provincia de Matanzas. Materiales y métodos: se realizó un estudio descriptivo-retrospectivo en 47 pacientes con cirrosis hepática de etiología viral, atendidos en el Servicio de Gastroenterología del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas, de enero de 2016 a enero de 2018. Los resultados de las variables analizadas se expusieron en tablas de doble entrada. Resultados: el 68,1 % de los pacientes correspondió a cirrosis por virus C. Predominaron los mayores de 50 años, con carga viral entre 4-6,9 log10, y atendidos en régimen ambulatorio. En el 57,4 % se detectaron signos endoscópicos de hipertensión portal, que se corroboraron en el doppler hepático. La ascitis asociada a diferentes sepsis fueron las complicaciones más registradas. El 55,4 % fue clasificado como Child-Pugh A, y el 76,6 % en etapa clínica compensada. Conclusiones: el diagnóstico y seguimiento de la cirrosis hepática viral sigue siendo un verdadero reto para la comunidad médica. De ahí los esfuerzos que han de realizarse para su control desde las fases compensadas, para retardar la aparición de complicaciones (AU).

ABSTRACT Introduction: viral etiology liver cirrhosis is an impacting health problem around the world, not only because of its high prevalence rate but also because of the costs generated by its medical care. Objective: to determine the behavior of the patients with viral etiology liver cirrhosis in the province of Matanzas. Materials and methods: a descriptive-retrospective study was carried out in 47 patients with viral etiology liver cirrhosis treated in the service of Gastroenterology of the Hospital "Comandante Faustino Perez" of Matanzas, from January 2016 to January 2018. The results of the analyzed variables were shown in double-entry tables. Results: 68.1% of the patients presented cirrhosis caused by C virus, Patients elder 50 years old predominated, with 4-6.9 log10, treated in ambulatory regimen. Endoscopic signs of portal hypertension were found in 57.4%. It was corroborated with liver Doppler. Ascites associated to different sepsis were the most frequently registered complications. 55.4% were classified as Child-Pugh A, and 76.6% were in compensated clinical stage. Conclusions: viral liver cirrhosis diagnosis and follow-up is still a true challenge for the medical community, and hence the efforts that should be made to control it from the compensated stages to delay the appearance of complications (AU).

Papel da imunohistoquímica no diagnóstico diferencial do carcinoma hepatocelular precoce e dos nódulos com displasia de alto grau em pacientes com cirrose / Results of immunohistochemistry in the differential diagnosis of early hepatocellular carcinoma and nodules with high-grade dysplasia in patients with cirrhosis

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary cancer of the liver and cirrhosis is considered a pre-malignant disease. In this context, the evolutionary sequence from low grade dysplastic nodule and high grade dysplastic nodule (HGDN) to early HCC and advanced HCC has been studied. The differential diagnosis between HGDN and early HCC is still a challenge, especially in needle biopsies OBJECTIVE: To evaluate an immunohistochemistry panel to differentiate dysplastic nodules and HCC. METHODS: Patients with cirrhosis who underwent surgical resection or liver transplantation were included. The sensitivity, specificity and accuracy for the diagnosis of neoplasia were analyzed by evaluating five markers: heat shock protein 70, glypican 3, glutamine synthetase, clathrin heavy chain and beta-catenin. P≤0.05 was considered statistically significant. RESULTS: One hundred and fifty-six nodules were included; of these, 57 were HCC, 14 HGDN, 18 low grade dysplastic nodules and 67 regenerative macronodules. Sensitivity of HCC diagnosis was 64.9% for glypican 3 and 77.2% for glutamine syntetase, while specificity was 96.0% and 96.0% respectively. When the panel of four markers was considered (excluding beta catenin), the specificity ranged from 87.9% for one positive marker to 100% for at least three markers. The best accuracy for HCC diagnosis was obtained with at least two positive markers, which was associated with a sensitivity of 82.5% and specificity of 99%. CONCLUSION: Differential diagnosis of dysplastic nodules and HCC by morphological criteria can be challenging. Immunomarkers are useful and should be used for the differential diagnosis between HCC and HGDN.

RESUMO CONTEXTO: O carcinoma hepatocelular (CHC) é o câncer primário do fígado mais frequente e a cirrose é considerada uma doença pré-maligna. Nesse contexto, a sequência evolutiva do nódulo displásico de baixo grau e nódulo displásico de alto grau (NDAG) para CHC precoce e CHC avançado tem sido estudada. O diagnóstico diferencial entre NDAG e CHC precoce ainda é um desafio, principalmente em biópsias por agulha. OBJETIVO: Avaliar um painel de imunohistoquímica para diferenciar nódulos displásicos de CHC. MÉTODOS: Foram incluídos pacientes com cirrose submetidos à ressecção cirúrgica ou transplante de fígado. A sensibilidade, especificidade e acurácia para o diagnóstico da neoplasia foram analisadas avaliando cinco marcadores: proteína de choque térmico 70kDa, glipican 3, glutamina sintetase, clatrina de cadeia pesada e beta-catenina. P≤0,05 foi considerado estatisticamente significativo. RESULTADOS: Cento e cinquenta e seis nódulos foram incluídos; destes, 57 eram CHC, 14 NDAG, 18 nódulos displásicos de baixo grau e 67 macronódulos regenerativos. A sensibilidade do diagnóstico de CHC foi de 64,9% para glipican 3 e 77,2% para glutamina sintetase, enquanto a especificidade foi de 96,0% e 96,0%, respectivamente. Quando o painel de quatro marcadores foi considerado (excluindo beta catenina), a especificidade variou de 87,9% para um marcador positivo a 100% para pelo menos três marcadores. A melhor acurácia para o diagnóstico de CHC foi obtida com pelo menos dois marcadores positivos, o que foi associado a uma sensibilidade de 82,5% e especificidade de 99%. CONCLUSÃO: O diagnóstico diferencial de nódulos displásicos e CHC por critérios morfológicos pode ser desafiador. Imunomarcadores são úteis e devem ser usados para o diagnóstico diferencial entre CHC e NDAG.

Uso do Stroop EncephalApp para o screening de encefalopatia hepática mínima em pacientes cirróticos no sul do Brasil / Use of the stroop encephalapp for covert hepatic encephalopathy screening in cirrhotic patients in southern brazil

ABSTRACT BACKGROUND: Covert hepatic encephalopathy (CHE) is difficult to detect due to the lack of easily applicable screening tools. The Stroop EncephalApp is a smartphone application already validated for CHE screening. However, its applicability to the Brazilian population is not known. OBJECTIVE: To estimate the prevalence of CHE and evaluate the use of Stroop EncephalApp in a cirrhotic population in Brazil. METHODS: In this cross-sectional study, we evaluated 99 patients previously diagnosed with liver cirrhosis in a Private Hospital in Curitiba/PR. Patients were initially submitted to the mini mental state examination (MMSE) to exclude individuals with dementia. After, the Psychometric Hepatic Encephalopathy Score (PHES) test was performed and lastly, the Stroop EncephalApp test. Results were adjusted for age, sex and education levels to evaluate the accuracy of the app on detecting the disease, comparing its results with the gold standard method (PHES). Patients with one or more of the following were excluded: dementia, inadequate MMSE score, illiteracy, color blindness, history of drugs/alcohol abuse within the past 3 months and previous or actual episodes of encephalopathy. The statistical analysis was performed by SPSS 2.0 and the significance adopted by 5%. RESULTS: We included 82 individuals in the final analysis. Among these patients, 29 were diagnosed with CHE by the PHES test (35.36% prevalence) and 28 of those obtained equal diagnosis by the Stroop EncephalApp (96.6% sensitivity). A total of 53 patients obtained negative results for CHE by PHES, while the Stroop test classified 27 of them as having the disease. In the multivariate analysis, high levels of education were associated with better performance during the tests. No significant relationship was observed between age and sex with the probability of diagnosing CHE through the PHES test.

RESUMO CONTEXTO: A encefalopatia hepática mínima (EHM) é uma complicação neuro-psiquiátrica da cirrose cuja detecção é dificultada pela falta de ferramentas práticas. O Stroop EncephalApp é um aplicativo de smartphones capaz de detectar a doença, entretanto sua aplicabilidade na população brasileira ainda não é conhecida. OBJETIVO: Avaliar o uso do Stroop EncephalApp para diagnóstico e avaliação de EHM em uma população de pacientes cirróticos no Brasil. MÉTODOS: Através de um estudo observacional transversal, 99 indivíduos sabidamente cirróticos foram recrutados do ambulatório de hepatologia de um hospital privado em Curitiba/PR. Primeiramente, foram aplicados o mini exame do estado mental (MEEM) para excluir indivíduos com demência; após, foram aplicados o Escore Psicométrico da Encefalopatia Hepática (PHES), atual padrão-ouro para diagnóstico de EHM, e posteriormente o Stroop EncephalApp, ajustando para idade, sexo e anos de formação acadêmica, buscando avaliar a eficiência do aplicativo em detectar a doença e comparar seus resultados com o atual padrão-ouro. Foram excluídos do estudo indivíduos com demência, pontuação insuficiente no MEEM, analfabetos, daltônicos, e com histórico de abuso de álcool/drogas ilícitas nos últimos 3 meses e paciente com episódios prévios ou atuais de encefalopatia hepática. A análise estatística foi realizada pelo SPSS 2.0 e a significância adotada em 5%. RESULTADOS: Um total de 82 indivíduos foram incluídos na análise final. Destes, 29 foram diagnosticados com EHM (35,36% de prevalência) através do PHES e 28 obtiveram o mesmo resultado após a aplicação do Stroop (96,6% de sensibilidade). Cinquenta e três pacientes obtiveram um resultado negativo para EHM através do PHES, sendo que 27 desses obtiveram um resultado positivo para EHM através do Stroop. Na análise multivariada, níveis elevados de escolaridade estiveram associados com melhor desempenho durante a execução dos testes. Não houve associação significativa entre idade e sexo com a probabilidade de apresentar encefalopatia através do PHES. CONCLUSÃO: O Stroop EncephalApp é uma ferramenta viável e com boa sensibilidade para o screening de EHM, mas possui baixa especificidade na população estudada.

Manifestaciones clínico-endoscópicas del paciente cirrótico / Clinical-endoscopic manifestations of the cirrhotic patient

RESUMEN Introducción: la cirrosis es un proceso dinámico y actualmente se conoce que cuando se elimina el agente primario de agresión que ha producido la cirrosis, se puede llegar a remitir la fibrosis. En Cuba la enfermedad representa la décima causa de muerte, con una tendencia ascendente en los últimos 20 años y una tasa de 13,4 por 100 000 habitantes. Objetivo: caracterizar clínica y endoscópicamente a pacientes con diagnóstico de cirrosis hepática. Material y método: se realizó un estudio descriptivo transversal, en el período comprendido entre los años 2017 - 19, donde el universo y la muestra quedaron constituidos por todos los pacientes mayores de 18 años ingresados con diagnóstico de cirrosis hepática. Resultados: predominó el sexo masculino en la sexta década de la vida, siento la principal causa el alcoholismo, caracterizado por manifestaciones generales, que en muchos casos debutan por complicaciones, apareciendo várices esofágicas en el 75 % de los casos, aunque gados I y II de Paquet, dependiente a un diagnóstico precoz de la enfermedad. Conclusiones: el alcoholismo crónico es la causa más frecuente de cirrosis hepática, debuta de forma frecuente por sus complicaciones, aunque el diagnóstico se hace en etapas precoces, con varices esofágicas incipientes (AU).

Summary Introduction: liver cirrhosis is a dynamic process and currently it is known that, when the primary agent of aggression that has produced the cirrhosis is eliminated, the fibrosis could remit. In Cuba, this diseases is the tenth cause of death, with an increasing tendency in the last twenty years and a rate of 13.4 per 100 000 inhabitants. Objective: to characterize, clinically and endoscopically, patients with hepatic cirrhosis diagnosis. Material and methods: a cross-sectional descriptive study was carried out, in the period 2017 - 2019, where the universe and the sample were formed by all the patients aged more than 18 years who entered the hospital with diagnosis of liver cirrhosis. Results: in this paper, male patients in their sixties predominated, being alcoholism the main cause of disease, characterized by general manifestations; patients debuted due to complications, appearing esophageal varices in 75 % of the cases, although Paquet I and II grades, in dependence to a disease precocious diagnosis. Conclusions: the authors concluded that chronic alcoholism is the most frequent cause in hepatic cirrhosis, almost always debuting by its complications, though the diagnosis is made in precocious stages, with emerging esophageal varices (AU).

Diagnóstico de hepatitis autoinmune / Diagnosis of autoimmune hepatitis

La hepatitis autoinmune es una enfermedad inflamatoria del hígado de etiología desconocida, que se caracteriza por la presencia de autoanticuerpos y niveles altos de globulinas séricas. Afecta a ambos sexos, a todos los grupos de edad, y se ha descrito en todas las razas. Tiene una amplia variedad de presentación clínica, lo que la convierte en un reto diagnóstico para el médico. La forma de presentación más común es la hepatitis aguda; sin embargo, un porcentaje no despreciable de pacientes es asintomático y hasta el 40% de los casos tiene cirrosis al momento del diagnóstico. El diagnóstico se basa en: 1) la medición de autoanticuerpos, como los antinucleares (ANA), los antimúsculo liso (ASMA), y los antimicrosomales de hígado y riñón (anti-LKM-1); 2) la detección de niveles séricos elevados de globulinas (especialmente IgG); 3) descartar otras etiologías de hepatitis crónica; y, 4) los hallazgos histológicos, los cuales además de confirmar el diagnóstico, ayudan a establecer la severidad. Se han desarrollado escalas y puntajes diagnósticos que permiten una mejor aproximación a dicha patología sin reemplazar el juicio del médico, por lo que deben ser interpretados bajo un adecuado contexto clínico. Un diagnóstico apropiado puede permitir el inicio oportuno de tratamiento con el fin de disminuir la progresión y el desarrollo de complicaciones.

Autoimmune hepatitis is an inflammatory disease of the liver of unknown etiology. It is characterized by the presence of autoantibodies and elevated levels of serum globulins. It affects both genders, all age groups and has been described in all races. It has a wide variety of clinical manifestations, so it remains a diagnostic challenge for physicians. The most common form of manifestation is acute hepatitis, however a non-negligible percentage of patients is asymptomatic, and up to 40% of cases have cirrhosis at the time of diagnosis. The diagnosis is based on: 1) measurement of autoantibodies, such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), and liver/kidney microsomal type 1 antibodies (anti-LKM-1); 2) detection of elevated serum levels of globulins (especially IgG); 3) exclusion of other causes of chronic hepatitis; and, 4) histological findings, which also confirm the diagnosis and help determine its severity. Diagnostic scales and scores have been developed to allow a better approach to this pathology without replacing the clinical judgment, so they must be interpreted under an adequate clinical context. A proper diagnosis can allow a timely initiation of treatment in order to decrease the progression and the development of complications.

Non-invasive methods for diagnosis of liver fibrosis: a systematic approach / Métodos não invasivos para o diagnóstico de fibrose hepática: uma abordagem sistemática

Introduction: Liver fibrosis is one of the most hazardous consequences of chronic liver diseases. Its early diagnosis is important for a quick decision making in the treatment and prognosis. Also, diagnosis and monitoring are usually performed by liver biopsies, a laborious method with high chances of complications and a subjective interpretation of results. Objectives: The research for the development of non-invasive methods are wide. The objective of this study is disclosing and evaluating some of said methods. Materials and methods: Validation articles were analyzed in four databases (Medline, Cochrane, LILACS and SciELO). Using the following terms: (liver fibrosis) AND (non-invasive diagnosis). All articles succeeded to inclusion and exclusion methods. Results: A couple of methods have pointed out promising results, in summary being much better used in the later diagnosis of liver fibrosis. Discussion: Many methods have been or are still in process of validation, some of which are promising, although they require future refinements in their evaluations, such as the diversification of the study population and evaluation of several chronic liver diseases. Conclusions: There are still various difficulties over the creation and standardization of analytical methods. However, existence and validation are important for a favorable future in the diagnosis of fibrosis.

Introdução: A fibrose hepática é uma das consequências graves de doenças hepáticas crônicas. Seu diagnóstico precoce é de suma importância para uma tomada rápida de decisão para tratamento e prognóstico. Seu diagnóstico e monitoramento costuma ser realizado por biópsias hepáticas, método custoso, com grandes chances de complicações e interpretação de resultados de forma subjetiva. Objetivos: A pesquisa para o desenvolvimento de métodos não invasivos é grande. O objetivo deste estudo é mostrar e avaliar alguns desses métodos. Materiais e métodos: Foram analisados artigos de validação em quatro bases de dados (Medline, Cochrane, LILACS e SciELO). Os termos empregados foram: (liver fibrosis) AND (non invasive diagnosis).Todos os trabalhos sucederam aos métodos inclusão e exclusão. Resultados: Alguns métodos se mostraram promissores, sendo grande parte utilizados no diagnóstico mais tardio da fibrose hepática. Discussão: Muitos métodos foram e estão sendo validados, alguns se mostrando promissores, embora necessitem de futuros refinamentos em suas avaliações, como diversificação da população estudada e avaliação em diversas doenças hepáticas crônicas. Conclusões: Ainda existem muitas dificuldades para criação e padronização dos métodos analíticos. Todavia, a existência e a validação são passos importantes para um futuro favorável no diagnóstico de fibrose.

Síndrome de Alagille / Alagille syndrome

Resumen Introducción: El síndrome de Alagille es una enfermedad con múltiples afectaciones, es autosómica dominante, con expresividad variable. Se identifica por manifestaciones hepáticas, vertebrales, cardiacas, oculares y dismorfia facial. Objetivo: Reportar un caso de S. de Alagille con afectación hepática, que debuta con hemorragia de vías digestivas altas. Materiales y métodos: Reporte de caso clínico confrontando con artículos de revisiones de temas en búsqueda electrónica en bases de datos de RIMA, MEDLINE, PUBMED, MEDSCAPE, de 1993-2018. Resultado: Paciente de 2 años, con diagnóstico tardío de enfermedad hepática, con progresión a cirrosis y hallazgos al examen físico que confirman Síndrome de Alagille. Se confirma el diagnóstico molecular coincidiendo con el principal hallazgo genético con anomalías asociadas al gen Jagged 1 (JAG1) localizado en el cromosoma 20 y el NOTCH2 del cromosoma 1. Conclusiones: Es de gran importancia resaltar esta patología infrecuente la cual representa un reto diagnóstico, debe tenerse en cuenta la múltiple afectación orgánica por lo cual es fundamental un manejo interdisciplinario

Abstract Introduction: Alagille syndrome is a disease with multiple impairments, is autosomal dominant with variable expressivity. It is identified by manifestations of vertebral, liver, heart, eye and facial dysmorphia. Objective: Report a case of Alagille S. with hepatic involvement, debuting with hemorrhage of upper digestive tract. Materials and methods: Clinical case report confronting articles reviewing subjects in electronic search in RIMA databases, MEDLINE, PUBMED, MEDSCAPE, from 1993-2018. Result: 2 year old patient, with late diagnosis of liver disease, with progression to cirrhosis and physical exam findings that confirm Alagille Syndrome. Confirmed the diagnostic molecular coinciding with the main genetic finding which are anomalies associated with the gene Jagged 1 (JAG1) located on chromosome 20 and the NOTCH2 of chromosome 1. Conclusions: It is important to highlight this uncommon disease which poses a diagnostic challenge, multiple organic involvement must be taken into account by which an interdisciplinary management is essential.

Arritmias e alterações cardíacas no paciente cirrótico / Arrhythmias and cardiac alterations in the cirrhotic patient

No Brasil, a cirrose é um problema de saúde pública, que afeta aproximadamente 2 milhões de pessoas. As causas mais comuns são a doença hepática alcoólica, as hepatites virais e a doença hepática não alcoólica. A relação entre desordens cardíacas e hepatopatias é descrita na literatura, e a mais importante delas é o prolongamento do intervalo QT. A cirrose, independente de sua causa, é uma patologia frequentemente encontrada na população brasileira. Por este motivo, elucidar dados referentes às arritmias cardíacas em pacientes cirróticos é de grande importância dentro do estudo desta subpopulação. O objetivo deste artigo é fazer uma revisão de literatura com as informações referentes a epidemiologia, fisiopatologia, fatores de risco e prognóstico para as arritmias cardíacas em portadores de cirrose. (AU)

In Brazil, cirrhosis is a public health problem affecting approximately 2 million people. The most common causes are alcoholic liver disease, viral hepatitis, and non-alcoholic liver disease. The relationship between cardiac disorders and liver diseases is described in the literature, and the most important one is the QT interval prolongation. Cirrhosis, regardless of its causes, is a pathology that is frequently found in the Brazilian population. For this reason, elucidating data regarding cardiac arrhythmias in cirrhotic patients is of great importance within the study of this subpopulation. The aim of this article is to review the literature with information on the epidemiology, pathophysiology, risk factors, and prognosis for cardiac arrhythmias in patients with cirrhosis. (AU)

Cirrhose hépatique dans le service de médecine interne du CNHU de Cotonou (2011-2014) : aspects épidémiologiques, cliniques et évolutifs

L'épidémiologie de la cirrhose est en pleine évolution dans le monde. Le but de la présente étude était de rapporter les aspects sociodémographiques cliniques, étiologiques et évolutifs chez les porteurs de cirrhose. PATIENTS ET METHODES. Cette étude rétrospective portant sur des dossiers de patients hospitalisés était menée dans le service de médecine interne du Centre National Hospitalier et Universitaire de Cotonou de 2011 à 2014. RESULTATS. Sur 305 dossiers exploitables, une cirrhose était trouvée chez 68 patients (22.2% ; sex ratio 2.09 ; âge moyen 55 ±14 ans, niveau socioéconomique défavorisé 32cas ; 47%). La cirrhose était décompensée dans 100% des cas. Le mode de présentation était la décompensation sous forme d'ascite (58cas ;85.3%) l'ictère (36 ; 52.9%) le carcinome hépatocellulaire (29 ; 42.6%) et l'hémorragie digestive (17 cas ; 25%). Les principales étiologies étaient l'hépatite virale B (26 cas ; 38.2%) ou C (10cas ;14.7%), la consommation chronique d'alcool (23 cas ;33.8%) ou les causes indéterminées (14 cas ; 20.5%). L'hépatite B et l'alcool prédominaient chez les hommes de la cinquantaine tandis que l'HVC était préférentiellement trouvée chez les femmes de plus de 60 ans (8 cas /10). Sur le plan évolutif, un décès hospitalier était noté dans 14 cas (20.6%). CONCLUSION : Les cirrhoses post virales encore fréquentes sont appelées à décroitre avec la vaccination contre l'hépatite B et le traitement curatif des hépatites B et C. Cependant la lutte contre les causes toxiques(alcool), iatrogènes (médicaments, phytothérapie) et le syndrome métabolique demeure capitale pour diminuer la prévalence de la cirrhose au Bénin

Fibrose hepática congênita e venopatia portal obliterativa sem hipertensão portal - revisão da literatura com base em um caso assintomático / Congenital hepatic fibrosis and obliterative portal venopathy without portal hypertension - a review of literature based on an asymptomatic case

ABSTRACT The disease and the case reported here are relevant especially because of their varied clinical presentation, possibility of being associated with other disorders affecting several organs and possible differential diagnoses. Congenital Hepatic Fibrosis is an autosomal recessive disease due to mutation in the PKHD1 gene, which encodes the fibrocystin/polyductine protein. It is a cholangiopathy, characterized by varying degrees of periportal fibrosis and irregular proliferation of bile ducts. Affected patients are typically diagnosed in childhood, but in some cases the disease may remain asymptomatic for many years. The exact prevalence and incidence of the disease are not known, but it is consider a rare disease, with a few hundred cases described worldwide. It can affect all ethnic groups and occur associated with various hereditary and non-hereditary disorders. The clinical presentation is quite variable, with melena and hematemesis being initial symptoms in 30%-70% of the cases. More rarely, they may present episodes of cholangitis. The disease has been classified into four types: portal hypertension, cholestasis / cholangitis, mixed and latent. Diagnosis begins with imaging tests, but the definition is made by the histopathological sample. So far, there is no specific therapy that can stop or reverse the pathological process. Currently, the therapeutic strategy is to treat the complications of the disease.

RESUMO A patologia e o caso aqui reportados são relevantes especialmente devido sua variada apresentação clínica, possibilidade de estar associada com outras desordens acometendo diversos órgãos e pelos possíveis diagnósticos diferenciais. A fibrose hepática congênita é uma doença autossômica recessiva, devido mutação no gene PKHD1, que codifica a proteína fibrocistina/poliductina. É uma colangiopatia, caracterizada por variados graus de fibrose periportal e proliferação irregular de ductos biliares. Os pacientes acometidos são tipicamente diagnosticados na infância, mas em alguns casos a doença pode permanecer assintomática por muitos anos. Exatas prevalência e incidência da doença não são conhecidas, mas sabe-se que é uma doença bastante rara, com algumas centenas de casos descritos no mundo. Pode afetar todos grupos étnicos e ocorrer associada com diversas desordens hereditárias e não-hereditárias. A apresentação clínica é bastante variável, com melena e hematêmese sendo sintomas iniciais em 30%-70% dos casos. Mais raramente, podem apresentar episódios de colangite. A doença tem sido classificada em quatro tipos: hipertensão portal, colestática/colangite, mista e latente. O diagnóstico inicia com exames de imagem, mas a definição é feita pela amostra histopatológica. Até o momento, não há terapia específica que possa parar ou reverter o processo patológico e a estratégia terapêutica atual é tratar as complicações da doença.

Bioimpedância: nova abordagem para detecção não invasiva da fibrose hepática - estudo piloto / Bioimpedance: new approach to non-invasive detection of liver fibrosis - a pilot study

ABSTRACT BACKGROUND: Fibrosis are common structural hepatic change in patients with chronic hepatitis. Liver biopsy is the gold standard for determining the extent of liver fibrosis. Considering the technical difficulties and cost, improvements in non-invasive screening tools are greatly needed. Bioimpedance have been shown to be safe to evaluate tissue fibrosis. OBJECTIVE: To assess the utility of using monofrequential bipolar bioimpedance for the detection of severity of liver fibrosis consistent with chronic viral hepatitis C infections. METHODS: One hundred and ten patients were studied prospectively and formed two groups according to the lab tests results for the detection of HCV, ALT and AST: Group 1 Control (n=50 healthy patients with HCV negative and with ALT and AST values within the normal clinical range) and Group 2 Positive (n=60 patients positive for anti-HCV positive) which were biopsied. All patients underwent an examination with an Electro Sensor Complex, bioimpedance technology. To compare the groups 1 and 2, the ROC curves was used to determine the specificity and sensitivity of the bioimpedance to detect liver fibrosis. To identify liver fibrosis severity the Group 2 Positive was subdivided according to the liver biopsy results (Metavir fibrosis score) into: Sub Group 2A (F0-F1 n=25) - patients without or with minimal portal fibrosis and Sub Group 2B (F3-F4 n=20) patients with numerous septa/cirrhosis. A statistical analysis was conducted to analyze the bioimpedance data differences in delta of the conductance. RESULTS: From the comparison between Groups 1 and 2: 1) The delta value for conductance in the pathway representing the right foot-left hand minus left hand-right foot demonstrated a sensitivity of 85% and a specificity of 78% with a cutoff value ≤5 and P=0.0001. 2) For the comparison between Sub Group 2A (Metavir F0+F1) and Sub Group 2B (Metavir F3+F4), the neural network for the Electro Sensor Complex data demonstrated a sensitivity of 85% and a specificity of 72% with a cutoff probability >50% and P=0.001. AUCROC=0.81. CONCLUSION: Bioimpedance technology had good level sensitivity and acceptable specificity for detecting liver fibrosis using delta of the conductance. There is a potential for the use of bioimpedance technology as non-invasive approaches for screening of liver fibrosis.

RESUMO CONTEXTO: A fibrose é uma alteração hepática estrutural comum em pacientes com hepatite crônica. A biópsia hepática é o padrão ouro para determinar a extensão da fibrose hepática. Considerando as dificuldades técnicas e os custos, melhorias em ferramentas de rastreio não-invasivas são bastante necessárias. A tecnologia bioimpedância tem se mostrado ser segura para avaliar fibrose tecidual. OBJETIVO: Avaliar a utilidade do uso da bioimpedância bipolar para detectar a severidade da fibrose hepática compatível com a hepatite viral B e C. MÉTODOS: Cento e dez pacientes foram estudados, prospectivamente e dois grupos foram formados de acordo com os resultados dos testes laboratoriais para a detecção de HCV, ALT e AST: Grupo 1 Controle (n=50 pacientes saudáveis com HCV negativos e com valores de ALT e AST dentro do padrão de normalidade) e Grupo 2 Positivo (n=60 pacientes positivos para a infecção viral anti-VHC ou HBsAg positiva) que foram biopsiados. Todos os pacientes foram submetidos a um exame com o Electro Sensor Complex, que utiliza a bioimpedância bipolar. Para comparar os Grupos 1 e 2, a curva ROC foi utilizada para determinar a especificidade e sensibilidade da bioimpedância em detectar a fibrose hepática. Para identificar a severidade da fibrose hepática, o Grupo 2 Positivo foi subdividido de acordo com os resultados da biópsia (escore Metavir) em: Sub Grupo 2A (F0-F1 n=25 ) - pacientes sem ou com fibrose portal mínima e Sub Grupo 2B (F3-F4 n=20) pacientes com numerosos septos/cirrose. A análise estatística foi realizada para analisar as diferenças dos valores delta de condutância da bioimpedância. RESULTADOS: A comparação entre os Grupos 1 e 2 mostrou: 1) O valor delta de condutância na via do pé direito à mão esquerda menos o valor do delta da mão esquerda ao pé direito demonstrou uma sensibilidade de 85% e uma especificidade de 78%, com um valor de corte ≤5 e P=0,0001. 2). Na comparação entre o Sub Grupo 2A (Metavir F0+F1) e o Sub Grupo 2B (Metavir F3 + F4), a rede neural para os dados aferidos pelo Electro Sensor Complex demonstrou uma sensibilidade de 85% e uma especificidade de 72%, com um corte de probabilidade >50% P=0,001 e AUCROC=0,81. CONCLUSÃO: Bioimpedância apresentou boa sensibilidade e aceitável especificidade para a detecção da fibrose hepática utilizando o delta da condutância da bioimpedância. Existe um potencial para o uso da bioimpedância como abordagens não-invasivas para o rastreamento da fibrose hepática.

Is serum angiotensin converting enzyme level a useful non-invasive marker for liver fibrosis in patients with chronic hepatitis C?

Summary Objective: Chronic hepatitis C (CHC) continues to be a critical problem. The liver fibrosis score is the most valuable tool in determining treatment and prognosis. Liver biopsy is still considered a gold method but, due to unmet needs, new non-invasive markers are required. The aim of this study was to investigate any possible relationship between serum angiotensin-converting enzyme (ACE) levels and the stages of liver fibrosis in patients with CHC. Method: A total 100 CHC and 100 healthy subjects were enrolled in this study. The relationship between serum ACE level and the stages liver fibrosis was investigated using three different formats, as follows: (group [G]-I, classic Ishak's Score from F1 to F6; G-II, mild [F1-2], moderate [F3-4] and severe [F5-6]; G-III, mild [≤ F2] and advanced [F > 2]). The clinical usability of serum ACE level for both groups was also investigated. Results: Median serum ACE levels were higher in the healthy group than in CHC (42.5 [7-119] vs. 36 [7-91] U/I, p=0.002). There was no statistical difference among the three different fibrosis groups (G-I, G-II, G-III, p=0.797, p=0.986, and p=0.874) and no correlation between serum ACE level and the stages of liver fibrosis (r=0.026, p=0.923). The usability of serum ACE for evaluated patients with CHC and healthy subjects were calculated as 47% and 64%, respectively. Conclusion: Our study indicated that there is no relationship or correlation between serum ACE levels and stages of liver fibrosis in patients with CHC. The assessment of serum ACE level using genetically corrected reference values may provide more accurate results.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review

ABSTRACT Introduction and aim. Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. Material and methods. Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. Results. Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.

A Randomized Controlled Trial of Procedural Techniques for Large Volume Paracentesis

ABSTRACT Introduction. The aim of this study is to investigate large volume therapeutic paracentesis using either a z-tract or axial (coxial) technique in a randomized controlled trial. Materials and methods. In this randomized, single blind study, patients with cirrhosis undergoing outpatient therapeutic paracentesis were randomized to the z-tract or the modified angular (coaxial) needle insertion technique. Subject and procedure characteristics were compared between the groups with ascites leakage as quantified by need for dressing changes with standardized sized gauze pads as a primary endpoint and subject procedural discomfort, operator preference, and procedure complications as secondary endpoints. Results. 72 paracenteses were performed during the study period: 34 to the z-tract and 38 to the coaxial insertion technique. Following exclusions, a total of 61 paracenteses were analyzed: 30 using the z-tract technique and 31 using the coaxial technique. There were equal rates of post-procedural leakage of ascites between groups (13% in both groups, p = 1.00). Using the visual analog scale (0 - 100), there was a statistically significant increase in the subject reported pain score with the z-tract compared with the coaxial method [26.4 (95% CI 18.7 - 34.1) vs. 17.2 (95% CI 10.6 - 23.8), p = 0.04]. Mean physician rated procedure difficulty (1 - 5) was significantly higher for the z-tract vs. the coaxial technique [2.1 (95% CI 1.6 - 2.6) vs. 1.5 (95% CI 1.2 - 1.8), p = 0.04]. Conclusion. When compared to the z-tract technique, the coaxial insertion technique is superior during large volume paracentesis in cirrhosis patients.

Age-Standardized Mortality Rates Related to Cirrhosis in Brazil from 2000 to 2012: A Nationwide Analysis

ABSTRACT Background. Cirrhosis remains the most frequent liver-related cause of death worldwide and we aimed to evaluate its burden in Brazil from 2000 to 2012. Material and methods. The Brazilian National Death Registry was analyzed from 2000 to 2012. Death by cirrhosis was defined by the presence of I85, K73 and/or K74 ICD 10 codes in contributing or underlying causes of death on the death certificate (DC). Crude mortality rates were calculated as the ratio of the absolute number of deaths and the estimated population. Mortality rates were age-adjusted by the direct standardization method using the WHO standard population. Results. A total of 265,180 deaths where cirrhosis was mentioned on the DC [77% male, aged 56 years] occurred from 2000 to 2012. Cirrhosis codes were present in 46% of liver-related deaths and 2% of all deaths in this period. Despite an increase in the absolute number of deaths (n = 18,245 to 22,340), the age-standardized mortality rates (95%CI) decreased from 13.32 (13.16-13.48) to 11.71 (11.59-11.83) per 100,000 inhabitants from 2000 to 2012 (p < 0.001). This trend was not uniform across the country, with decreases in death rates in the South [14.46 (14.07-14.87) to 10.89 (10.59-11.19)] and Southeast [15.85 (15.6-16.09) to 12.52 (12.34-12.70)] and increases in the North [8.84 (8.24-9.43) to 11.53 (11.08-11.99)] and Northeast [9.41 (9.13-9.69) to 10.93 (10.68-11.17)] (p < 0.001 for all). Conclusion. Cirrhosis remains a major public health issue, despite the reduction in mortality rates in the last decade.