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INTRODUCTION AND OBJECTIVES: The increasing incidence of hepatocellular carcinoma (HCC) in China is an urgent issue, necessitating early diagnosis and treatment. This study aimed to develop personalized predictive models by combining machine learning (ML) technology with a demographic, medical history, and noninvasive biomarker data. These models can enhance the decision-making capabilities of physicians for HCC in hepatitis B virus (HBV)-related cirrhosis patients with low serum alpha-fetoprotein (AFP) levels. PATIENTS AND METHODS: A total of 6,980 patients treated between January 2012 and December 2018 were included. Pre-treatment laboratory tests and clinical data were obtained. The significant risk factors for HCC were identified, and the relative risk of each variable affecting its diagnosis was calculated using ML and univariate regression analysis. The data set was then randomly partitioned into validation (20 %) and training sets (80 %) to develop the ML models. RESULTS: Twelve independent risk factors for HCC were identified using Gaussian naïve Bayes, extreme gradient boosting (XGBoost), random forest, and least absolute shrinkage and selection operation regression models. Multivariate analysis revealed that male sex, age >60 years, alkaline phosphate >150 U/L, AFP >25 ng/mL, carcinoembryonic antigen >5 ng/mL, and fibrinogen >4 g/L were the risk factors, whereas hypertension, calcium <2.25 mmol/L, potassium ≤3.5 mmol/L, direct bilirubin >6.8 µmol/L, hemoglobin <110 g/L, and glutamic-pyruvic transaminase >40 U/L were the protective factors in HCC patients. Based on these factors, a nomogram was constructed, showing an area under the curve (AUC) of 0.746 (sensitivity = 0.710, specificity=0.646), which was significantly higher than AFP AUC of 0.658 (sensitivity = 0.462, specificity=0.766). Compared with several ML algorithms, the XGBoost model had an AUC of 0.832 (sensitivity = 0.745, specificity=0.766) and an independent validation AUC of 0.829 (sensitivity = 0.766, specificity = 0.737), making it the top-performing model in both sets. The external validation results have proven the accuracy of the XGBoost model. CONCLUSIONS: The proposed XGBoost demonstrated a promising ability for individualized prediction of HCC in HBV-related cirrhosis patients with low-level AFP.
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Carcinoma Hepatocelular , Cirrosis Hepática , Neoplasias Hepáticas , Aprendizaje Automático , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Cirrosis Hepática/sangre , Cirrosis Hepática/virología , Cirrosis Hepática/diagnóstico , Medición de Riesgo , Factores de Riesgo , China/epidemiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/sangre , Valor Predictivo de las Pruebas , Adulto , Nomogramas , Biomarcadores de Tumor/sangre , Hepatitis B/complicaciones , Hepatitis B/sangre , Hepatitis B/diagnóstico , Anciano , Estudios RetrospectivosAsunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , África del Sur del Sahara/epidemiología , África del Sur del Sahara/etnología , Europa (Continente)/epidemiología , Factores de Riesgo , Población Negra/estadística & datos numéricosAsunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , África del Sur del Sahara/epidemiología , África del Sur del Sahara/etnología , Europa (Continente)/epidemiología , Masculino , Factores de Riesgo , Femenino , Persona de Mediana Edad , Población Negra/estadística & datos numéricos , AdultoRESUMEN
BACKGROUND & AIMS: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown. METHODS: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain. We assessed the 5- and 10-year cumulative incidences of HCC in the overall study population, among different clinically relevant subgroups and across (m)PAGE-B subgroups. Next, we explored the different risk factors for HCC. RESULTS: During a median follow-up of 8 years, we analyzed 1,473 individuals of whom 34 developed HCC. The 5- and 10-year cumulative incidences of HCC were 1% and 2.4%. The 10-year cumulative incidence of HCC was 0.7% among individuals without advanced fibrosis at baseline, compared to 12.1% among individuals with advanced fibrosis (p <0.001). Higher age (adjusted hazard ratio [aHR] 1.05), lower platelet count (aHR 0.98), lower albumin level (aHR 0.90) and higher HBV DNA log10 (aHR 1.21) were significantly associated with HCC development. The 10-year cumulative incidence of HCC was 0.5% among individuals with a low PAGE-B score, compared to 2.9% in the intermediate- and 15.9% in the high-risk groups (p <0.001). CONCLUSIONS: In this unique international multicenter cohort of SSA and AS individuals with chronic hepatitis B, we observed 5- and 10-year cumulative HCC risks of 1% and 2.4%, respectively. The risk of HCC was negligible for individuals without advanced fibrosis at baseline, and among individuals with low baseline (m)PAGE-B scores. These findings can be used to guide HCC surveillance strategies. IMPACT AND IMPLICATIONS: Sub-Saharan African ethnicity has been associated with a higher risk of hepatocellular carcinoma among individuals with chronic hepatitis B. In this international multicenter cohort study of sub-Saharan African and Afro-Surinamese individuals living with chronic hepatitis B in Europe, we observed 5- and 10-year cumulative incidences of hepatocellular carcinoma of 1% and 2.4%, respectively. The risk was negligible among individuals without advanced fibrosis and a low baseline (m)PAGE-B score. These findings can be used to guide HCC surveillance strategies in this population.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/tratamiento farmacológico , Estudios de Cohortes , Estudios Retrospectivos , Estudios Transversales , Antivirales/uso terapéutico , Factores de Riesgo , Europa (Continente) , Fibrosis , África del Sur del Sahara/epidemiología , Virus de la Hepatitis B/genéticaRESUMEN
BACKGROUND & AIMS: The long-term impact of alcohol-related public health policies (PHPs) on disease burden is unclear. We aimed to assess the association between alcohol-related PHPs and alcohol-related health consequences. METHODS: We conducted an ecological multi-national study including 169 countries. We collected data on alcohol-related PHPs from the WHO Global Information System of Alcohol and Health 2010. Data on alcohol-related health consequences between 2010-2019 were obtained from the Global Burden of Disease database. We classified PHPs into five items, including criteria for low, moderate, and strong PHP establishment. We estimated an alcohol preparedness index (API) using multiple correspondence analysis (0 lowest and 100 highest establishment). We estimated an incidence rate ratio (IRR) for outcomes according to API using adjusted multilevel generalized linear models with a Poisson family distribution. RESULTS: The median API in the 169 countries was 54 [IQR 34.9-76.8]. The API was inversely associated with alcohol use disorder (AUD) prevalence (IRR 0.13; 95% CI 0.03-0.60; p = 0.010), alcohol-associated liver disease (ALD) mortality (IRR 0.14; 95% CI 0.03-0.79; p = 0.025), mortality due to neoplasms (IRR 0.09; 95% CI 0.02-0.40; p = 0.002), alcohol-attributable hepatocellular carcinoma (HCC) (IRR 0.13; 95% CI 0.02-0.65; p = 0.014), and cardiovascular diseases (IRR 0.09; 95% CI 0.02-0.41; p = 0.002). The highest associations were observed in the Americas, Africa, and Europe. These associations became stronger over time, and AUD prevalence was significantly lower after 2 years, while ALD mortality and alcohol-attributable HCC incidence decreased after 4 and 8 years from baseline API assessment, respectively (p <0.05). CONCLUSIONS: The API is a valuable instrument to quantify the robustness of alcohol-related PHP establishment. Lower AUD prevalence and lower mortality related to ALD, neoplasms, alcohol-attributable HCC, and cardiovascular diseases were observed in countries with a higher API. Our results encourage the development and strengthening of alcohol-related policies worldwide. IMPACT AND IMPLICATIONS: We first developed an alcohol preparedness index, an instrument to assess the existence of alcohol-related public policies for each country. We then evaluated the long-term association of the country's alcohol preparedness index in 2010 with the burden of chronic liver disease, hepatocellular carcinoma, other neoplasms, and cardiovascular disease. The strengthening of alcohol-related public health policies could impact long-term mortality rates from cardiovascular disease, neoplasms, and liver disease. These conditions are the main contributors to the global burden of disease related to alcohol use. Over time, this association has not only persisted but also grown stronger. Our results expand the preliminary evidence regarding the importance of public health policies in controlling alcohol-related health consequences.
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Alcoholismo , Carcinoma Hepatocelular , Enfermedades Cardiovasculares , Hepatopatías Alcohólicas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/complicaciones , Hepatopatías Alcohólicas/patología , Alcoholismo/complicaciones , Política Pública , Política de SaludRESUMEN
â¢Chronic hepatitis B is a well-defined risk factor for hepatocellular carcinoma, and it is important to implement early detection programs for hepatocellular carcinoma in affected patients. In this study, the data found suggest that the mPAGE-B score can be applied to reduce the number of medical consultations in young patients infected with the hepatitis B virus and aged <40 years. 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. Results - 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.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Antivirales/uso terapéutico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiología , Estudios Retrospectivos , Estudios Transversales , Virus de la Hepatitis B , Cirrosis Hepática/complicacionesRESUMEN
INTRODUCTION AND OBJECTIVES: We initiated this multicenter study to integrate important risk factors to create a nomogram for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) for clinician decision-making. PATIENTS AND METHODS: Between April 2011 and March 2022, 2281 HCC patients with an HBV-related diagnosis were included. All patients were randomly divided into two groups in a ratio of 7:3 (training cohort, n = 1597; validation cohort, n = 684). The nomogram was built in the training cohort via Cox regression model and validated in the validation cohort. RESULTS: Multivariate Cox analyses revealed that the portal vein tumor thrombus, Child-Pugh class, tumor diameter, alanine aminotransferase level, tumor number, extrahepatic metastases, and therapy were independent predictive variables impacting overall survival. We constructed a new nomogram to predict 1-, 2-, and 3-year survival rates based on these factors. The nomogram-related receiver operating characteristics (ROC) curves indicated that the area under the curve (AUC) values were 0.809, 0.806, and 0.764 in predicting 1-, 2-, and 3-year survival rates, respectively. Furthermore, the calibration curves revealed good agreement between real measurements and nomogram predictions. The decision curve analyses (DCA) curves demonstrated excellent therapeutic application potential. In addition, stratified by risk scores, low-risk groups had longer median OS than medium-high-risk groups (p < 0.001). CONCLUSIONS: The nomogram we constructed showed good performance in predicting the 1-year survival rate for HBV- related HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Virus de la Hepatitis B , Nomogramas , Neoplasias Hepáticas/etiología , Área Bajo la CurvaRESUMEN
Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Factores de Riesgo , FibrosisRESUMEN
BACKGROUND: Conflicting data regarding the incidence of hepatocellular carcinoma (HCC) after cure of HCV infection with direct-acting antivirals (DAAs) remains. We investigated the incidence and risk factors to HCC after treatment with DAAs followed up for five years. METHODS: A total of 1075 HCV patients ≥ 18 years were treated with DAAs from 2015 to 2019 and followed until 2022. Ultrasonography was performed before DAAs and each 6 months thereafter. RESULTS: Of the total, 51/1075 (4.7%) developed HCC in the median of 40 (IQR 25-58) months: 26/51 (51%) male, median age 60 (IQR 54-66) years, alpha-fetoprotein (AFP) 12.2 (IQR 6.1-18.8) ng/mL, 47/51 (92.1%) cirrhotic 78.7%, 8/51 (15.7%) without sustained virological response (SVR). Seventeen percent had non-characterized nodules before DAAs. Cumulative HCC incidence was 5.9% in 5 years. Overall incidence was 1.46/100 patient-years (PY) (95% CI = 1.09-1.91), being 2.31/100 PY (95% CI = 1.70-3.06), 0.45/100 PY (95% CI = 0.09-1.32) and 0.20/100 PY (95% CI 0.01-1.01) in METAVIR F4, F3 and F2, respectively, and the main risks to HCC were non-characterized nodule, cirrhosis, high AFP values and non-SVR. CONCLUSION: HCV cure reduced risk for HCC, but it still occurred particularly in cirrhotic patients. Some risk factors can be identified to predict early HCC diagnosis.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/diagnóstico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Antivirales/uso terapéutico , alfa-Fetoproteínas , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/diagnóstico , Incidencia , Factores de Riesgo , Cirrosis Hepática/diagnóstico , Hepatitis C/tratamiento farmacológicoRESUMEN
Non-alcoholic fatty liver disease is growing in worldwide prevalence and thus, is expected to have a higher number of NAFLD-related hepatocellular carcinoma (HCC) in the following years. This review describes the risk factors associated with HCC in NAFLD-patients. The presence of liver cirrhosis is the preponderant one. Male gender, PNPLA3 variants, diabetes, and obesity also appear to predispose to the development of HCC, even in non-cirrhotic subjects. Thus far, intensive lifestyle modifications, including glycemic control, and obesity treatment, are effective therapies for NAFLD/ non-alcoholic steatohepatitis and, therefore, probably, also for HCC. Some drugs that aimed at decreasing inflammatory activity and fibrosis, as well as obesity, were studied. Other data have suggested the possibility of HCC chemoprevention. So far, however, there is no definitive evidence for the routine utilization of these drugs. We hope, in the future, to be able to profile patients at higher risk of NAFLD-HCC and outline strategies for early diagnosis and prevention.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Masculino , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/prevención & control , Carcinoma Hepatocelular/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/diagnóstico , Factores de Riesgo , Cirrosis Hepática/complicaciones , Obesidad/complicacionesRESUMEN
Hepatitis B virus (HBV) is intrinsically oncogenic and related to hepatocellular carcinoma (HCC). Predictive scores of HCC have been developed but have been poorly studied in admixed populations. Therefore, we aimed to evaluate the performance of PAGE-B and mPAGE-B scores for HCC prediction in HBV Brazilian patients and factors related to HCC occurrence. This is a retrospective study that evaluated patients followed at a tertiary university center. A total of 224 patients were included, with a median follow-up period of 9 years. The mean age at HBV diagnosis was 38.71 ± 14.19 years, predominantly males (66.1%). The cumulative incidence of HCC at 3, 5, and 7 years was 0.993%, 2.70%, and 5.25%, respectively, being related in the univariate logistic regression analysis to male sex (p = 0.0461), older age (p = 0.0001), cirrhosis at HBV diagnosis (p < 0.0001), and higher values of PAGE-B and mPAGE-B scores (p = 0.0002 and p < 0.0001, respectively). Older age, male sex, and cirrhosis at HBV diagnosis were independently associated with HCC occurrence. The AUROCs of PAGE-B and mPAGE-B were 0.7906 and 0.7904, respectively, with no differences between them (p = 0.9767). In conclusion, both PAGE-B and mPAGE-B showed a correct prediction of HCC above 70% in this cohort.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Brasil/epidemiología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Femenino , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Risk factors for HCC include hepatitis C (HCV) and B (HBV) virus infection, alcoholic cirrhosis and genetic alterations that can affect several cellular pathways. OBJECTIVE: This study purposed to analyze the gene and serum protein expression of vascular endothelial growth factor (VEGF), angiogenesis, alpha fetoprotein, cystatin B (CSTB), ß-catenin and glypican-3 (GPC3) in groups with HCC, cirrhosis or HCV and controls, and their relation with clinical staging in the HCC and cirrhosis groups, as well its sensitivity and specificity values. METHODS: A total of 230 individuals were distributed in Group 1 (G1) - 80 patients with HCC; Group 2 (G2) - 76 patients with cirrhosis due to any etiology; Group 3 (G3) - 33 patients with HCV; Group 4 (G4 - controls) - 41 individuals without clinical or biochemical signs of any liver disease. Gene expression was analyzed by qRT-PCR and serum proteins were performed using the ELISA method. RESULTS: Increased VEGF and angiogenesis, alpha fetoprotein expression could be observed in BCLC stage-D patients compared to stage-B patients, and stage-C patients showed higher expression of ß-catenin, compared to stage-B patients (P<0.05). For VEGF and GPC3, discriminatory power was observed between HCC patients and controls (AUC =0.71; 0.82, respectively). CSTB showed discriminatory power in the comparison between patients with HCV and controls (AUC =0.74). CONCLUSION: The present study confirms the sensitivity of serum CSTB in the diagnosis of hepatitis C, and gene expression of VEGF and serum GPC3, confer both sensitivity and specificity for the diagnosis of HCC.
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Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/genética , Glipicanos/genética , Hepacivirus , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/genética , Factor A de Crecimiento Endotelial Vascular , alfa-Fetoproteínas/análisis , beta CateninaRESUMEN
RATIONALE: Lysosomal acid lipase deficiency (LAL-D) is a poorly diagnosed genetic disorder characterized by the accumulation of cholesteryl esters and triglycerides in many tissues, leading to dyslipidemia and cardiovascular complications. In the liver, deposits are found within hepatocytes and Kupffer cells, generating microvesicular steatosis, progressive fibrosis, and cirrhosis. Sebelipase alfa is the target therapy which can improve laboratory changes and reduce the progression of liver damage, but this is not yet widely available. PATIENT CONCERNS: We are reporting a 15-year follow-up of a Brazilian man who was diagnosed with cirrhosis at age 43 and with LAL-D at age 53, but he has never been treated with sebelipase alfa for economic reasons. During the coronavirus disease 2019 (COVID-19) pandemic, he lost follow-up and missed three 6-month ultrasound exams for liver cancer screening. DIAGNOSIS: At age 58, a remarkable deterioration in liver function was observed and he was diagnosed with hepatocellular carcinoma (HCC) outside the Milan Criteria (two nodules measuring 48mm and 25mm). Three other individuals with LAL-D and progression to liver cancer have been reported so far and none of them underwent enzyme replacement therapy: an 11-year-old girl with HCC, a 51-year-old male with cholangiocarcinoma, and a 21-year-old male with hepatocellular-cholangiocarcinoma. The latter had the same mutation in the gene LIPA as our patient, but a relationship between this variant and malignancies has not yet been established. LESSONS: We emphasize how important is to treat LAL-D patients after diagnosis in order to avoid worsening liver function and progression to neoplasms. Untreated individuals should be considered at a higher risk but the most appropriate liver cancer screening program for this subgroup is still unknown.
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COVID-19 , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Adulto , Carcinoma Hepatocelular/etiología , Niño , Ésteres del Colesterol , Femenino , Humanos , Cirrosis Hepática , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Triglicéridos , Enfermedad de Wolman , Adulto Joven , Enfermedad de WolmanRESUMEN
Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Consenso , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Enfermedad del Hígado Graso no Alcohólico/epidemiologíaRESUMEN
BACKGROUND: Evaluate the role of liver stiffness measurement (LSM) by transient elastography (TE) as a risk factor for hepatocellular carcinoma (HCC) occurrence in a prospective cohort of Brazilian hepatitis C virus (HCV) patients with cirrhosis. METHODS: A cohort of 99 consecutive HCV patients was included between 2011 and 2016 with baseline LSM ≥12 kilopascals (kPa). Baseline variables were evaluated and HCC occurrence was documented. Kaplan-Meier methods with a log-rank test and the use of cox univariate and multivariate analysis assessed the association between variables and clinical results. RESULTS: The mean age was 57.8±10.6 years. In a follow-up over a mean of 3.3 years, 20 (20.2%) patients developed HCC. In univariate logistic regression analysis, variables associated with HCC occurrence were: lower platelet count (P=0.0446), higher serum alpha-fetoprotein (P=0.0041) and bilirubin (P=0.0008) values, higher Model for End-Stage Liver Disease (MELD) score (P=0.0068) and higher LSM (P=0.0354). LSM evaluated by TE was independently associated with HCC development, and the best cut-off value for higher HCC risk was >21.1 kPa (HR: 5.548; 95%CI: 1.244-24.766; P=0.025). CONCLUSION: A high value of liver stiffness relates substantially to an increased risk for HCC occurrence in Brazilian patients with cirrhosis due to HCV.
Asunto(s)
Carcinoma Hepatocelular , Diagnóstico por Imagen de Elasticidad , Enfermedad Hepática en Estado Terminal , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Anciano , Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Diagnóstico por Imagen de Elasticidad/efectos adversos , Diagnóstico por Imagen de Elasticidad/métodos , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la EnfermedadAsunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Humanos , Hígado/patología , Cirrosis Hepática/patología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patologíaRESUMEN
Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Consenso , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Enfermedad del Hígado Graso no Alcohólico/epidemiologíaRESUMEN
This study aims to evaluate the accuracy of the PAGE-B and REACH-B scores in predicting the risk of developing HCC in patients with chronic hepatitis B regularly followed up at a reference service in the State of Maranhão. A historical, longitudinal, retrospective cohort study, carried out from the review of medical records of patients with chronic Hepatitis B. PAGE-B and REACH-B scores were calculated and the accuracy of the scores in predicting the risk of HCC in the studied population was evaluated. A total of 978 patients were included, with a median age of around 47 years, most of them female and not cirrhotic. HCC was identified in 34 patients. Thrombocytopenia, high viral load, male gender and age were associated with the occurrence of HCC. The ROC curve for the PAGE-B score showed a value of 0.78 and for the REACH-B score of 0.79. The cutoff point for PAGE-B was 11 points for greater sensitivity and for REACH-B 7.5 points considering greater sensitivity and 9.5 points considering greater specificity. PAGE-B and REACH-B scores were able to predict the risk of developing HCC in the studied population. The use of risk stratification scores is useful to reduce costs associated with HCC screening.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Antivirales/uso terapéutico , Brasil/epidemiología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Femenino , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
MicroRNAs (miRNAs), which are regarded as crucial regulators of gene expression and diverse aspects of cell biology, can be present in various body fluids as highly stable molecules. It is also known that miRNAs exert tissue-specific regulation of gene transcription. Large amount of clinical and experimental evidence provided the rationale for raising the intriguing question of whether miRNAs can mediate cell-cell communication. For those reasons, miRNAs have been considered as the 'Holy Grail' of biomarkers allowing non-invasive diagnostic screening and early detection of a variety of diseases, including solid and non-solid cancers. In a study published in Clin. Sci. (Lond.) (2011) 120(5):183-193 (https://doi.org/10.1042/CS20100297), Gui et al. investigated the hypothesis that circulating miRNAs could be used to identify patients with liver pathologies. Specifically, the authors profiled circulating miRNAs in patients with hepatocellular carcinoma (HCC), liver cirrhosis (LC), and healthy controls and found that serum miR-885-5p levels were significantly higher in samples of patients with HCC (6.5-fold increase) and LC (8.8-fold increase). In this commentary, we highlight biological aspects associated with mir-122-the 'liver-specific' miRNA, which has been associated with a diverse range of liver pathologies. In addition, we discuss the relevance of mir-885-5p as potential biomarker for detecting human cancers. Finally, we provide some clues about how presumably unrelated miRNAs such as miR-122 and miR-885-5p may act in similar biological processes (BPs), making the miRNA regulatory networks more complex than anticipated.
Asunto(s)
Neoplasias Hepáticas/etiología , MicroARNs/fisiología , Animales , Biomarcadores de Tumor , Ensamble y Desensamble de Cromatina , Humanos , Ratones , MicroARNs/análisis , MicroARNs/sangreRESUMEN
INTRODUCTION AND OBJECTIVES: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. PATIENTS: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. RESULTS: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023). CONCLUSIONS: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.