Noninvasive assessment of liver fibrosis can predict clinical outcomes at late follow-up after a sustained virological response in HCV patients?

OBJECTIVES: The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. METHODS: A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. RESULTS: At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. CONCLUSION: Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism.

INTRODUCTION: Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics. METHODS: We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed. RESULTS: Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity. CONCLUSION: Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.

18F-FDG PET/CT AS AN ASSESSMENT TOOL OF HEPATOCELLULAR CARCINOMA SECONDARY TO NON-ALCOHOLIC FATTY LIVER DISEASE DEVELOPMENT IN EXPERIMENTAL MODEL.

BACKGROUND: Hepatocellular carcinoma (HCC) can be the last step of non-alcoholic fatty liver disease (NAFLD) evolution. Experimental models are crucial to elucidate the pathogenesis of HCC secondary to NAFLD. The 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating HCC development and progression. OBJECTIVE: To standardize the imaging method of PET/CT with 18F-FDG as an evaluation tool of the experimental model of HCC secondary to NAFLD. METHODS: Ten male Sprague-Dawley rats were fed with choline-deficient high-fat diet and diethylnitrosamine (DEN) in the drinking water for 16 weeks and then received 1 mL of saline solution (0.9%) daily by gavage for three weeks. At the 16th and 19th weeks, abdominal ultrasonography (USG) was performed. 18F-FDG PET/CT images were obtained before the beginning of experiment (week 0) and at the end (week 19). Histological and immunohistochemically analysis were also performed. RESULTS: The USG results showed a homogeneous group at the 16th week with an average of 4.6±2.74 nodules per animal. At the 19th week, PET/CT findings demonstrated an average of 8.5±3.7 nodules per animal. The mean values of SUVmed and SUVmax were 2.186±0.1698 and 3.8±1.74, respectively. The average number of nodules per animal in the histological analysis was 5.5±1.5. From all nodules, 4.6% were classified as well-differentiated HCC and 81.8% were classified as poorly-differentiated HCC. CONCLUSION: 18F-FDG PET/CT was able to evaluate the development of HCC in an experimental model of NAFLD non-invasively. From the standardization of PET/CT in this model, it is possible to use this tool in future studies to monitor, in vivo and non-invasively, the progression of HCC.

PET/CT com 18F-FDG como ferramenta de avaliação do desenvolvimento de carcinoma hepatocelular secundário a doença hepática gordurosa não alcoólica em modelo experimental / 18f-fdg pet/ct as an assessment tool of hepatocellular carcinoma secondary to non-alcoholic fatty liver disease development in experimental model

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) can be the last step of non-alcoholic fatty liver disease (NAFLD) evolution. Experimental models are crucial to elucidate the pathogenesis of HCC secondary to NAFLD. The 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating HCC development and progression. OBJECTIVE: To standardize the imaging method of PET/CT with 18F-FDG as an evaluation tool of the experimental model of HCC secondary to NAFLD. METHODS: Ten male Sprague-Dawley rats were fed with choline-deficient high-fat diet and diethylnitrosamine (DEN) in the drinking water for 16 weeks and then received 1 mL of saline solution (0.9%) daily by gavage for three weeks. At the 16th and 19th weeks, abdominal ultrasonography (USG) was performed. 18F-FDG PET/CT images were obtained before the beginning of experiment (week 0) and at the end (week 19). Histological and immunohistochemically analysis were also performed. RESULTS: The USG results showed a homogeneous group at the 16th week with an average of 4.6±2.74 nodules per animal. At the 19th week, PET/CT findings demonstrated an average of 8.5±3.7 nodules per animal. The mean values of SUVmed and SUVmax were 2.186±0.1698 and 3.8±1.74, respectively. The average number of nodules per animal in the histological analysis was 5.5±1.5. From all nodules, 4.6% were classified as well-differentiated HCC and 81.8% were classified as poorly-differentiated HCC. CONCLUSION: 18F-FDG PET/CT was able to evaluate the development of HCC in an experimental model of NAFLD non-invasively. From the standardization of PET/CT in this model, it is possible to use this tool in future studies to monitor, in vivo and non-invasively, the progression of HCC.

RESUMO BACKGROUND: O carcinoma hepatocelular (CHC) pode ser a última fase da doença hepática gordurosa não alcoólica (DHGNA). Modelos experimentais são cruciais para elucidação da patogênese do CHC secundário a DHGNA. A tomografia por emissão de pósitrons/tomografia computadorizada (PET/TC) com 2-desoxi-2-(18F)fluoro-D-glicose (18F-FDG) desempenha um importante papel na avaliação do desenvolvimento e progressão do CHC. OBJETIVO: Padronizar a metodologia de imagem por PET/TC com 18F-FDG como uma ferramenta de avaliação do modelo experimental de CHC secundário a DHGNA. MÉTODOS: Dez ratos Sprague-Dawley machos foram alimentados com dieta hiperlipídica deficiente em colina associada a dietilnitrosamina (DEN) na água de beber por 16 semanas e depois receberam 1 mL de solução salina (0,9%) por gavagem diariamente por três semanas. Nas 16ª e 19ª semanas, foi realizada a ultrassonografia abdominal. As imagens do PET/TC com 18F-FDG foram obtidas antes do início do experimento (semana 0) e no final (semana 19). Análises histológica e imunohistoquímica também foram realizadas. RESULTADOS: Os resultados da ultrassonografia demonstraram um grupo homogêneo na 16ª semana com uma média de 4,6±2,74 nódulos por animal. Na 19ª semana, os achados do PET/CT demonstraram uma média de 8,5±3,7 nódulos por animal. Os valores médios de SUVmed e SUVmáx foram 2,186±0,1698 e 3,8±1,74, respectivamente. A média do número de nódulos na análise histológica foi de 5,5±1,5. De todos os nódulos, 4,6% foram classificados como bem diferenciados e 81,8% foram classificados como CHC pouco diferenciado. CONCLUSÃO: O PET/TC com 18F-FDG foi capaz de avaliar o desenvolvimento do CHC secundário a DHGNA de forma não invasiva. A partir da padronização do PET/CT neste modelo, faz-se possível a utilização desta ferramenta em futuros estudos para monitorar, in vivo e de forma não invasiva, a progressão do CHC.