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Introducción. La enfermedad hepática esteatósica asociada a disfunción metabólica (MASLD) se ha convertido en la enfermedad hepática crónica más frecuente en los países occidentales, causando un aumento en los costos y en la ocupación hospitalaria. La caracterización integral previa al trasplante hepático en pacientes con MASLD es una gran interrogante, especialmente en nuestro medio. El objetivo del presente estudio fue realizar la caracterización clínico-epidemiológica de pacientes trasplantados por cirrosis hepática (CH) descompensada o carcinoma hepatocelular (CHC) asociado a MASLD. Metodología. Se desarrolló un estudio observacional retrospectivo, descriptivo, de corte transversal en el Servicio de Hepatología del Hospital Pablo Tobón Uribe en Medellín, Colombia. Se incluyeron pacientes mayores de 17 años, con diagnóstico de CH o de CHC asociado a MASLD que fueron trasplantados entre los años 2004 a 2017. Resultados. Se encontraron 84 pacientes que fueron trasplantados con esas características. La edad promedio de los pacientes fue de 59±10,5 con una mayor proporción significativa de hombres sobre mujeres, llegando casi al 70 %. Con relación a las comorbilidades, se encontró que el sobrepeso/obesidad, la hipertensión arterial y la diabetes mellitus tipo 2 fueron un hallazgo en el 44,1 %, 33,3 % y 33,3 %, respectivamente. Por otro lado, el 14,5 %, el 33,7 % y el 51,8 % presentaron un Child-Pugh A, B y C, respectivamente. La media del puntaje MELD fue de 18,9±6,26. Con respecto a las complicaciones de la cirrosis, el 77,4 % de los pacientes presentó ascitis, el 61,9 % encefalopatía hepática, el 36,9 % hemorragia del tracto digestivo superior y el 29,8 % peritonitis bacteriana espontánea. Conclusión. Los resultados expuestos mostraron nuestra experiencia en trasplante hepático en pacientes con CH y CHC asociado a MASLD. Se debe realizar una evaluación multidisciplinaria antes y después del trasplante en estos pacientes, haciendo especial énfasis en el manejo de la disfunción metabólica y sus componentes, entre los que se destacan la obesidad y la diabetes mellitus.
Introduction. Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most frequent chronic liver disease in Western countries, causing increased costs and hospital occupancy. The comprehensive pre-transplant characterization in patients with MASLD is a major question, especially in our setting. The aim of the present study was to perform the clinical-epidemiological characterization of transplanted patients with decompensated liver cirrhosis (LC) or hepatocellular carcinoma (HCC) associated with MASLD. Methodology. A retrospective, descriptive, cross-sectional observational study was carried out in the Hepatology Department of the Pablo Tobón Uribe Hospital in Medellin, Colombia. Patients over 17 years of age, with a diagnosis of LC or HCC associated with MASLD who were transplanted between 2004 and 2017 were included. Results. We found 84 patients who were transplanted with these characteristics. The mean age of the patients was 59±10.5 with a significantly higher proportion of men over women, reaching almost 70%. Regarding comorbidities, overweight/obesity, arterial hypertension, and type 2 diabetes mellitus were found in 44.1%, 33.3%, and 33.3%, respectively. On the other hand, 14.5%, 33.7%, and 51.8% had Child-Pugh A, B, and C, respectively. The mean MELD score was 18.9±6.26. Regarding complications of cirrhosis, 77.4% of patients developed ascites, 61.9% hepatic encephalopathy, 36.9% upper gastrointestinal tract hemorrhage, and 29.8% spontaneous bacterial peritonitis. Conclusion. The above results showed our experience of liver transplantation in patients with LC and HCC associated with MASLD. A multidisciplinary evaluation should be performed before and after transplantation in these patients, with special emphasis on the management of metabolic dysfunction and its components, including obesity and diabetes mellitus.
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Non-alcoholic Fatty Liver DiseaseABSTRACT
ABSTRACT BACKGROUND: The effect of weight loss (WL) on histopathological aspects of non-alcoholic fatty liver disease (NAFLD) may provide further insights into the dynamics of hepatic recovery after WL. OBJECTIVE: To analyze the effects of pre-operative WL on insulin resistance- and NAFLD-related histology in individuals undergoing bariatric surgery (BS) with or without pre-operative WL. DESIGN AND SETTING: A matched cross-sectional study was conducted at a public university hospital and a private clinic in Campinas, Brazil. METHODS: An analytical, observational, cross-sectional study was conducted using prospectively collected databases of individuals who underwent BS and liver biopsy at either a public tertiary university hospital (with pre-operative WL) or a private clinic (without pre-operative WL). Random electronic matching by gender, age, and body mass index (BMI) was performed and two paired groups of 24 individuals each were selected. RESULTS: Of the 48 participants, 75% were female. The mean age was 37.4 ± 9.6. The mean BMI was 38.9 ± 2.6 kg/m2. Fibrosis was the most common histopathological abnormality (91.7%). Glucose was significantly lower in the WL group (92 ± 19.1 versus 111.8 ± 35.4 mg/dL; P = 0.02). Significantly lower frequencies of macrovesicular steatosis (58.3% versus 95.8%; P = 0.004), microvesicular steatosis (12.5% versus 87.5%; P < 0.001), and portal inflammation (50% versus 87.5%; P = 0.011) were observed in the WL group. CONCLUSION: Pre-operative WL was significantly associated with lower frequencies of macro- and mi- crovesicular steatosis, portal inflammation, and lower glycemia, indicating an association between the recent trajectory of body weight and histological aspects of NAFLD.
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Transarterial chemoembolization （TACE） is currently the primary treatment method for advanced liver cancer. This article elaborates on the current status of application of TACE in hepatocellular carcinoma from the aspects of existing techniques， patient selection， and efficacy assessment and summarizes the research advances and prospects of TACE combined with local treatment and systemic therapy， so as to provide new ideas for clinical practice and experimental studies.
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ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl4） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl4 was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G0/G1 phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G0/G1 phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G0/G1 phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.
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Abstract Objective: To evaluate the degree of tumor necrosis after transarterial chemoembolization (TACE), used as a bridging therapy in patients awaiting liver transplantation, and its effect on survival. Materials and Methods: This was a retrospective cohort study involving 118 patients submitted to TACE prior to liver transplantation, after which the degree of tumor necrosis in the explant and post-transplant survival were evaluated. Results: Total necrosis of the neoplastic nodule in the explant was observed in 76 patients (64.4%). Of the patients with total necrosis in the explanted liver, 77.8% had presented a complete response on imaging examinations. Drug-eluting bead TACE (DEB-TACE), despite showing a lower rate of complications than conventional TACE, provided a lower degree of total necrosis, although there was no statistical difference between the two. By the end of the study period, 26 of the patients had died. Survival was longer among the patients with total necrosis than among those with partial or no necrosis (HR = 2.24 [95% CI: 0.91-5.53]; p = 0.078). Conclusion: In patients undergoing TACE as a bridging therapy, total tumor necrosis appears to be associated with improved patient survival.
Resumo Objetivo: Avaliar os resultados da necrose tumoral após quimioembolização transarterial (TACE) como terapia ponte e seu reflexo na sobrevida dos pacientes. Materiais e Métodos: Estudo de coorte retrospectivo, com 118 pacientes que realizaram TACE, em que foram avaliados o grau de necrose tumoral no explante e a sobrevida pós-transplante. Resultados: Necrose total do nódulo neoplásico no explante foi observada em 76 pacientes (64,4%). Observou-se que 77,8% dos pacientes com necrose total no explante hepático tinham apresentado resposta completa nos exames de imagem. A DEB-TACE, apesar de ter demonstrado menor taxa de intercorrências, proporcionou menor grau de necrose total em relação à TACE convencional, a despeito de não haver diferença estatística. Ao final do seguimento do estudo, o número de óbitos foi de 26. A sobrevida foi maior nos pacientes que tiveram necrose total quando comparada com grau de necrose parcial ou ausência de necrose [HR = 2,24 (IC 95%: 0,91-5,53); p = 0,078]. Conclusão: Necrose completa do tumor nos pacientes submetidos a TACE como terapia ponte parece estar associada com melhora da sobrevida.
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Background: A disintegrin and metalloproteinases (ADAMs) have emerged as therapeutic targets in many cancers. ADAM10 was particularly studied in hepatocellular carcinoma (HCC) for its potential role in hepatocarcinogenesis and HCC progression. Objective: To investigate the immunohistochemical (IHC) expression of ADAM10 in HCCs and the adjacent noncancerous tissues from 70 HCC patients, attempting to elucidate any association between ADAM10 and HCC development and/or progression. Materials and Methods: IHC staining for anti-ADAM10 was performed using horseradish peroxidase technique. An extent and intensity-dependent scoring was applied dividing samples into high- and low-expression groups. HCCs were statistically compared in relation with gender, age, cirrhosis, hepatitis C virus (HCV) status, alpha-fetoprotein (AFP) serum level, tumor size, multiplicity, encapsulation/invasion, grade, histological pattern and variant, mitosis, necrosis, vascular emboli, portal thrombosis, stage, recurrence, and mortality. Kaplan–Meier's method was used to analyze disease-free and overall survival (DFS and OS). Results: ADAM10 was expressed in 77.1% of HCCs compared with 42.9% of noncancerous tissues. Differential expression showed significant statistical difference (P = 0.02), as 38.6% of HCCs showed high expression, whereas 92.8% of noncancerous samples showed low expression. No significant differences were observed when high- and low-ADAM10 expression HCCs were compared with respect to all tested prognostic parameters except the HCV status. Patients whose tumors showed high-ADAM10 expression had relatively longer DFS and OS times, but with insignificant log-rank differences. Conclusions: ADAM10 is frequently expressed in HCCs compared with noncancerous hepatic tissues suggesting its role in hepatocarcinogenesis, especially in association with HCV. It has no association with HCC progression or survival. Further studies should be sought to investigate its validity as a therapeutic target.
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ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.
RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.
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Fibrolamellar hepatocellular carcinoma is a rare primary hepatic tumor that usually occurs in youth. The common presenting features are vague abdominal pain, nausea, vomiting and weight loss. We present a case report of a young male who presented with cholestatic jaundice and on evaluation was diagnosed to have fibrolamellar hepatocellular carcinoma. He underwent successful surgical resection of the tumor. In young individuals presenting with unexplained cholestasis, fibrolamellar hepatocellular carcinoma should be considered.
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Background: Diagnosis of hepatocellular carcinoma (HCC) is difficult on morphology alone in poorly differentiated tumors and metastatic carcinomas. Appropriate immunohistochemical markers are required for definite diagnosis. In this article, we have analyzed the histopathological and immunohistochemical features of HCC and elucidate the best possible immunohistochemistry (IHC) marker combination by comparing the sensitivity of various markers in different grades of tumor. Methods: A total of 116 consecutive cases were analyzed retrospectively. The hematoxylin and eosin stained sections were reviewed in all the cases. IHC was done using hepatocellular specific antigen (HSA), arginase?1, glypican?3, and polyclonal carcinoembryonic antigen (pCEA). The sensitivity of various immunohistochemical markers individually as well as in combination for different tumor grades was determined. Results: Histologically, the predominant subtype comprised of classic variant (109,93.9%) followed by combined hepatocellular and cholangiocarcinoma (4,3.4%) and fibrolamellar variant (3,2.6%). Trabecular pattern was the most common histological pattern. On grading, 65,56.03% were moderately differentiated, 34,29.31% well differentiated, and17, 14.65% poorly differentiated. HSA and polyclonal?CEA showed higher sensitivity than arginase?1 and glypican?3 in well and moderately differentiated tumors. In contrast arginase?1 and glypican?3 showed better sensitivity in poorly differentiated HCC. The overall sensitivity increased to greater than 90% if HSA/polyclonal?CEA is combined with either arginase?1/glypican?3 irrespective of tumor grade. Conclusion: Majority of the tumors were classic variants and moderately differentiated. HSA along with either arginase?1 or glypican?3 is the best combination of immunomarker for identification of hepatocellular differentiation irrespective of tumor grade.
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ABSTRACT Background: Persistent hepatitis B virus (HBV) infection can lead to hepatocellular carcinoma (HCC) alone, that is, without the development of previous cirrhosis, which makes it of paramount importance to predict the risk patients with chronic hepatitis B have for developing HCC in the future. Thus, the mPAGE-B score was developed in order to predict very low risks of HCC, becoming an important score, since with low risk, patient surveillance can be spread out. Objective: The main objective of this study was to predict the risk of HCC according to the mPAGE-B score for patients with chronic hepatitis B, using antiviral therapy. Methods: A cross-sectional, descriptive, quantitative, and retrospective study was conducted. Patients with chronic hepatitis B from the Hepatology Outpatient Clinic of the Federal University of the Fronteira Sul/HCPF in Passo Fundo, Rio Grande do Sul, covering a period of 12 years, were analyzed. Results: Of the 67 patients submitted to data collection, the mean age at diagnosis was 51.4 (±12.1) years, with a predominance of males (76.1%-n.51). All patients were HBeAg negative at diagnosis and 11 (16.4%) had cirrhosis. Regarding the antiviral regimen, 70.1% used tenofovir disoproxil fumarate (TDF) and 29.9% entecavir (ETV). According to m-PAGE-B stratification, 18 (25%) patients were classified as low-risk, 30 (41.7%) as intermediate-risk, and 19 (26.4%) as high-risk of developing HCC. The probability of developing HCC of these 67 patients in 3 years was 0.4% for low, 2.8% for moderate, and 9% for high risk. In 5 years, the probability was 0.5% for low, 4.4% for moderate, and 14% for high risk. Conclusion: This study demonstrates that the mPAGE-B score can be applied to decrease the number of consultations of patients with chronic hepatitis B in specialized outpatient clinics and, based on this population, patients aged ≤40 years may have one consultation per year instead of semi-annual.
RESUMO Contexto: A infecção persistente do vírus da hepatite B (HBV) pode levar ao carcinoma hepatocelular (CHC) de forma independente, ou seja, sem o desenvolvimento de cirrose anteriormente, o que torna de suma importância predizer o risco que os pacientes com hepatite B crônica têm para desenvolver CHC no futuro. Assim, o escore mPAGE-B surgiu com o intuito de prever riscos baixos de CHC, tornando-se um escore de extrema relevância, uma vez que diante de risco baixo, pode-se espaçar a vigilância do paciente. Objetivo: O principal objetivo deste trabalho é predizer o risco de CHC, conforme o escore mPAGE-B, para os pacientes com hepatite B crônica em uso de terapia antiviral. Métodos: Foi realizado um estudo transversal, descritivo, quantitativo e retrospectivo. Foram analisados pacientes com hepatite B crônica do ambulatório de hepatologia, da Universidade Federal da Fronteira Sul/HCPF, em Passo Fundo, no Rio Grande do Sul, abrangendo um período de 12 anos. Resultados: Dos 67 pacientes submetidos à coleta de dados, a média de idade no diagnóstico foi 51,4 (±12,1) anos, com uma predominância do sexo masculino (76,1%-n.51). Todos os pacientes eram HBeAg negativos no diagnóstico e 11 (16,4%) tinham cirrose. Conforme a estratificação do mPAGE-B, 18 pacientes (25%) foram classificados como de baixo risco, 30 (41,7%) como risco intermediário, e 19 (26,4%) como alto risco de desenvolver CHC. A probabilidade de desenvolver CHC desses 67 pacientes em 3 anos é de 0,4% para risco leve, 2,8% para moderado e 9% para alto. Em 5 anos, a probabilidade é de 0,5% para risco leve, 4,4% para moderado e 14% para alto. Conclusão: Este estudo demonstra que o mPAGE-B pode ser um escore aplicado para diminuir o número de consultas de pacientes com hepatite B crônica em ambulatórios especializados e, baseado nessa população, talvez os pacientes com idade ≤40 anos possam ter uma consulta por ano ao invés de ser semestralmente.
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RESUMEN La hemorragia hepática espontánea (HHE) es una afección rara que resulta de una lesión en el parénquima hepático producida sin una causa externa. Presentamos el caso de una mujer de 74 años que, durante una internación por reagudización de su enfermedad pulmonar obstructiva crónica (EPOC), desarrolla episodio de hemorragia hepática espontánea que evoluciona a shock hemorrágico. Se realiza cirugía con resección atípica de carcinoma hepatocelular (HCC) con hemorragia activa en segmento III hepático. La paciente responde al tratamiento inicial, pero a los 16 días posoperatorios fallece en Unidad de Terapia Intensiva (UTI) debido a una afección respiratoria.
ABSTRACT Spontaneous hepatic hemorrhage (SHH) is a rare condition resulting from a breach in the hepatic parenchyma that occurs without an external cause. We report the case of a 74-year-old woman who, while being hospitalized due to exacerbation of chronic obstructive pulmonary disease (COPD), presented an episode of SHH with hemorrhagic shock. She underwent atypical resection of a hepatocellular carcinoma (HCC) with active bleeding in liver segment III. The patient had a favorable response to the initial treatment but died in the intensive care unit (ICU) on postoperative day 16 due to a respiratory tract complication.
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RESUMEN La captación de 18 FDG en PET-TC por un adenoma hepatocelular (HCA) es poco frecuente. Esta situación genera dudas en cuanto a los diagnósticos diferenciales y tratamiento. El objetivo de este artículo fue realizar una mini revisión de los últimos 37 años de HCA con avidez por el 18FDG y presentar un nuevo caso. Sobre la base de un estudio realizado por otros autores entre 1984 y 2014, se amplía la búsqueda utilizando las mismas palabras clave hasta el año 2021. Se analizan los datos relevantes. Entre 1984 y 2021 detectamos 38 casos en 37 años. Fue más frecuente en mujeres en edad reproductiva. Los subtipos H-HCA e I-HCA fueron los más frecuentes. El tratamiento quirúrgico fue el más empleado. La diferenciación celular y los trastornos metabólicos de la glucosa y de los lípidos favorecerían la captación de 18FDG. La resección hepática ofrecería mayores garantías permitiendo el estudio completo de la lesión.
ABSTRACT Hepatocellular adenoma (HCA) uptake of 18FDG uptake on PET-CT is rare. This situation poses doubts about the differential diagnoses and treatment. The aim of this article is to perform a mini review of 18FDG avid HCA over the past 37 years and to describe a new case presentation. Based on a study conducted by other authors between 1984 and 2014, we extended the search until 2021 using the same keywords. The relevant data were analyzed. Between 1984 and 2021 we detected 38 cases in 37 years. HCAs were more common in women of childbearing age. The most common types were H-HCA an I-HCA. Surgical resection was the treatment most used. Cell differentiation and glucose and lipid metabolic diseases would favor 18FDG uptake. Liver resection provides better outcomes, allowing for a complete examination of the lesion.
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Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. Extrahepatic metastasis occurs mostly through the hematogenous route and is seen in around one-third of patients with the common sites of involvement being the lungs, regional lymph nodes, bone, adrenal glands, and pancreas. Soft-tissue metastasis from HCC is an extremely rare condition. Here, we present a rare case of an elderly male, with HCC presenting as a soft-tissue mass in the gluteal region. We further provide a detailed discussion regarding the investigative approach used to arrive at the diagnosis and the treatment modalities offered. Case reports like this may offer insight into the possibilities of such unusual presentations and aid the clinician in his endeavor to the early diagnose and treat the patient.
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Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and has a high death rate in the world. This research while examining the expression of OCT3 at the mRNA level has also studied gene methylation profile in patients with HCC in comparison with people without HCC. The volunteers were: patients with HCC (n=81) and a healthy control group (n=90). The expression of OCT3was studied using the qRT-PCR method. The methylation profile was evaluated by genomic DNA using methylation specific PCR (MSP) method. The expression level of OCT3 marker mRNA in patients has decreased significantly compared to healthy individuals (0.58 ± 0.311 vs 1.20 ± 0.355, P <0.001). No significant statistical relationship was found between demographic data and OCT3 expression in participants (P >0.05). The amount of methylation (UM + MM) in cancer patients has raised vs controls (P <0.001) and has increased the risk of cancer (OR=0.379, 95% CI=1.171-2.839, P <0.001, and OR=2.727, 95% CI=1.251-5.945, P <0.001, respectively).Changes in OCT3 levels appear to be associated with HCC. Also, changing the methylation pattern of this gene can reveal HCC pathology.
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Background: Primary hepatocellular carcinoma (HCC) is a major health hazard and frequent cause of liver cancers accounting 90% of cancers of liver worldwide. It has high mortality, prevalence, and incidence rate in Sub-Saharan, South Africa, and South-east Asia. Its etiology is associated with infection, dietary habits, and lifestyle factors. Aims and Objectives: The present study was designed to discuss the various possible etiologies for high incidence of HCC in Western Arunachal Pradesh, India. Materials and Methods: Data were collected as one among 33 population-based cancer registries in India under national cancer registry program of national center for disease informatics and research, Indian Council of Medical Research between 2012 and 2014 in Tomo Riba Institute of Health and Medical Sciences, Naharlagun. Data were represented in frequency and percentage using descriptive statistics. Results: With 194 cases, HCC represented 13.5% of overall malignancies in the region. It is 3 times more common in males than in females. Age-adjusted incidence rate for men was 21.44 and for women was 7.05. Conclusion: Western Arunachal Pradesh reported high incidence of hepatocellular carcinoma in the world. This finding may be associated with high prevalence of hepatitis and alcoholism in the region and perhaps also associated with local food habits.
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ABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.
RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.
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Objective: To investigate the therapeutic effect and mechanism of lenvatinib on regorafenib-resistant hepatocellular carcinoma cells. Methods: CCK-8 and clone formation assay were used to observe the inhibitory effect of lenvatinib on the growth of hepatocellular carcinoma cells. Flow cytometry was used to detect the apoptosis of regorafenib-resistant hepatocellular carcinoma cells treated with lenvatinib. The expression levels of related proteins were detected by western blot and immunohistochemical staining. The inhibitory effect of lenvatinib on the tumor formation ability of regorafenib-resistant hepatocellular carcinoma cells in vivo was observed by subcutaneous tumor formation experiment in mice. Results: CCK-8 and clone formation assay showed that lenvatinib could inhibit the proliferation of regorafenib-resistant hepatocellular carcinoma cells. The number of clones of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group (120.67±11.06, 53.00±11.14, 55.00±9.54, 78.67±14.64) were all lower than those in control group (478.00±24.52, 566.00±27.87, 333.67±7.02, 210.00±12.77, all P<0.05). Flow cytometry showed that lenvatinib could promote apoptosis of regorafenib-resistant hepatocellular carcinoma cells, the apoptosis rates of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group [(12.30±0.70)%, (9.83±0.38)%, (15.90±1.32)%, (10.60±0.00)%] were all higher than those in control group [(7.50±0.87)%, (5.00±1.21)%, (8.10±1.61)%, (7.05±0.78)%, all P<0.05]. The apoptosis-related protein levels suggested that apoptosis was increased in the treatment of lenvatinib. The animal study showed that lenvatinib can inhibit the growth of regorafenib-resistant cells in vivo. Immunohistochemistry and western blot results showed that lenvatinib could down-regulate the abnormally activated IGF1R/Mek/Erk signaling pathway in regorafenib-resistant cells. Conclusion: Lenvatinib can reverse regorafenib resistance in hepatocellular carcinoma, possibly by down-regulating IGF1R/Mek/Erk signaling pathway.
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Animals , Mice , Humans , Apoptosis , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Liver Neoplasms/pathology , Signal TransductionABSTRACT
In recent years, immune checkpoint inhibitors (ICIs) have emerged as a significant advancement in the treatment of advanced hepatocellular carcinoma (HCC), providing benefits to a subset of patients. At present, there are still many problems with ICIs treatment for HCC, such as limited objective remission rate, high treatment cost, frequent treatment-related adverse events, and tumor hyperprogression. In this context, it is important to find indicators that can predict the efficacy of ICIs treatment in order to optimize patients’ selection and maximize clinical benefits, further avoiding unnecessary toxic side effects and economic losses. This article discusses biochemical and cytological indicators, tumor-related markers, imaging indicators, and immune-related adverse events in order to guide clinical treatment.
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Objective:To investigate the expression of zinc finger protein 22 (ZNF22) gene in hepatocellular carcinoma (HCC) and its effect on tumor proliferation, apoptosis, invasion and metastasis of HCC.Methods:The expression of ZNF22 in 32 HCC specimens, and 371 HCC samples from the cancer genome atlas database were analyzed. ZNF22 knockdown and negative control SNU-449 and JHH-7 HCC cell lines were constructed. The effects of ZNF22 on HCC cells were observed by cell proliferation assay, plate clone formation assay, apoptosis assay, scratch healing assay, Transwell invasion assay, subcutaneous tumor formation, tail vein injection transfer, and small animal live imaging assay in nude mice.Results:The expression of ZNF22 gene is higher in HCC tissues than in paracellular carcinoma tissues, and the difference was statistically significant ( P<0.001). The growth rate of SNU-449 and JHH-7 cells in ZNF22 knockdown group was lower than that in control group, and the difference was statistically significant ( P<0.001). Compared with negative control group, the clone number formed by SNU-449 cells in ZNF22 knockdown group decreased (26±8 vs. 59±5, P<0.01), the level of apoptosis increased (6.60%±0.22% vs. 2.38%±0.30%, P<0.001), the migration rate decreased (14.47%±6.42% vs. 68.84%±8.01%, P<0.001), and the number of invasive cells decreased (48.00±2.23 vs. 179.00±4.81, P<0.001). There was no obvious tumor growth after subcutaneous injection of JHH-7 cells into nude mice in ZNF22 knockdown group, and the systemic fluorescence expression was lower than that of the negative control group, and the difference was statistically significant ( P<0.05). No metastases were observed on autopsy in knockdown group nude mice. Conclusion:ZNF22 is highly expressed in HCC while knockdowing ZNF22 gene inhibited the growth, proliferation, invasion, metastasis of HCC cells, and induced apoptosis of HCC cells.
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Objective:To establish and validate a preoperative differentiateon model of intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular carcinoma (CHC) based on the inflammatory markers and conventional clinical indicators.Methods:The clinical data of 116 patients with ICC or CHC admitted to Henan Provincial People's Hospital from January 2018 to March 2023 were retrospectively analyzed, including 74 males and 42 females, aged (58.5±9.4) years old. The data of 83 patients were used to establish the differentiation model as the training group, including 50 cases of ICC and 33 cases of CHC. The data of 33 patients were used to validate the model as the validation group, including 20 cases of ICC and 13 cases of CHC. The clinical data including the platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), prognostic inflammatory index (PII), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were collected and analyzed. The receiver operating characteristic (ROC) curve was used to analyze the best cut-off values of PLR, SII, PII, PNI, NLR and LMR. Univariate and multivariate logistic regression analysis were used to determine the differential factors between ICC and CHC. The R software was used to draw the nomogram, calculate the area under the curve (AUC) to evaluate the model accuracy, and draw the calibration chart and the decision curve to evaluate the predictive efficacy of the model.Results:Univariate logistic regression analysis showed that liver cirrhosis, history of hepatitis, alpha fetoprotein, carbohydrate antigen 199, gamma-glutamyltransferase (GGT), PLR, PNI and inflammation score (IS) could be used to differentiate ICC from CHC (all P<0.05). The indicators identified in univariate analysis were included in multivariate logistic regression analysis. The results showed that absence of liver cirrhosis, GGT>60 U/L, PNI>49.53, and IS<2 indicated the pathology of ICC (all P<0.05). Based on the above four factors, a nomogram model was established to differentiate the ICC and CHC. The AUC of ROC curve of the nomogram model in the training and validation groups were 0.851 (95% CI: 0.769-0.933) and 0.771 (95% CI: 0.594-0.949), respectively. The sensitivities were 0.760 and 0.750, and the specificities were 0.818 and 0.769, respectively. The calibration chart showed that the predicted curve fitted well to the reference line. The decision curve showed that the model has a clear positive net benefit. Conclusion:The nomogram model based on inflammatory markers showed a good differentiation performance of ICC and CHC, which could benefits the individualized treatment.