Background: HCC is a major cause of cancer death worldwide. Serum biomarkers such as alpha-fetoprotein (AFP), protein induced by vitamin K absence-II, and the Gender, Age, AFP-L3, AFP, Des-gamma-carboxy prothrombin (GALAD) score have been recommended for HCC surveillance. However, inconsistent recommendations in international guidelines limit their clinical utility. Methods: In this multicenter study, over 2000 patient samples were collected in 6 Latin American and 2 European countries. The performance of the GALAD score was validated in cirrhotic cases, and optimized versions were tested for early-stage HCC and prediagnostic HCC detection. Results: The GALAD score could distinguish between HCC and cirrhosis in Latin American patients with an AUC of 0.76, sensitivity of 70%, and specificity of 83% at the conventional cutoff value of −0.63. In a European cohort, GALAD had an AUC of 0.69, sensitivity of 66%, and specificity of 72%. Optimizing the score in the 2 large multicenter cohorts revealed that AFP-L3 contributed minimally to early-stage HCC detection. Thus, we developed a modified GALAD score without AFP-L3, the ASAP (age, sex, AFP, and protein induced by vitamin K absence-II), which showed promise for early-stage HCC detection upon validation. The ASAP score also identified patients with cirrhosis at high risk for advanced-stage HCC up to 15 months before diagnosis (p < 0.0001) and differentiated HCC from hemangiomas, with a specificity of 100% at 71% sensitivity. Conclusion: Our comprehensive analysis of large sample cohorts validates the GALAD score’s utility in Latin American, Spanish, and Dutch patients for early-stage HCC detection. The optimized GALAD without AFP-L3, the ASAP score, is a good alternative and shows greater promise for HCC prediction.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The STAT4 rs7574865 genetic variant has been associated with an increased risk of developing HCC in Asian populations. However, this association has not been studied in Latin America and is poorly assessed in European populations. This case-control study investigated the association between STAT4 rs7574865 and HCC risk in these populations. We evaluated DNA samples from seven medical institutions across six Latin American countries and one Dutch institution in 1060 individuals (344 HCC and 716 controls). STAT4 rs7574865 SNP was genotyped using TaqMan-genotyping assay and analyzed using logistic regression. We found no significant association between the homozygous risk allele (G) of STAT4 and HCC development in either population, with odds ratios (OR) for GG versus TT of 0.85 (CI: 0.48–1.52, p = 0.58) and 0.81 (CI: 0.34–1.93, p = 0.67) for Latin Americans and Europeans respectively. No correlation was found between the risk allele and HCC based on underlying liver disease. However, we found that Latin Americans of European ancestry were more likely to carry the risk allele. Our results suggest that the STAT4 SNP rs7574865 does not influence the risk of developing HCC in Latin American or European populations, highlighting the importance of evaluating genetic risk factors in various ethnic groups and understanding the possible influence of ancestry on the genetic basis of disease.

Este documento de consenso, desarrollado por la Sociedad Ecuatoriana de Cardiología, establece un marco integral para el diagnóstico y tratamiento de la hipertensión pulmonar (HP). La HP se define hemodinámicamente por una presión arterial pulmonar media (PAPm) superior a 20 mmHg, medida mediante cateterismo cardíaco derecho (CCD). Es fundamental diferenciar el compromiso pre y poscapilar utilizando parámetros como la presión en cuña pulmonar (PCP) y la resistencia vascular pulmonar (RVP). Una PCP > 15 mmHg indica un origen en las cavidades izquierdas del corazón (poscapilar), mientras que una RVP > 2 UW sugiere una enfermedad vascular pulmonar (precapilar). La clasificación de la HP, basada en los criterios de la OMS, es crucial para un tratamiento adecuado y se divide en cinco grupos principales:Grupo 1: Hipertensión arterial pulmonar (HAP), que incluye formas idiopáticas y hereditarias.Grupo 2: HP asociada a enfermedad cardíaca izquierda, la causa más común.Grupo 3: HP debida a enfermedades pulmonares crónicas y/o hipoxia, como la EPOC.Grupo 4: HP tromboembólica crónica (HPTEC), causada por obstrucciones arteriales.Grupo 5: HP con mecanismos poco claros o multifactoriales.El diagnóstico sigue un algoritmo escalonado que comienza con la historia clínica y el examen físico ante síntomas como la disnea de esfuerzo. Los pasos iniciales incluyen estudios no invasivos como electrocardiograma, radiografía de tórax y análisis de sangre (incluyendo BNP/NT-proBNP). La ecocardiografía es la herramienta no invasiva clave para evaluar la probabilidad de HP. Pruebas adicionales como la tomografía computarizada (TC) y la gammagrafía de ventilación/perfusión (V/Q) ayudan a identificar causas subyacentes, como la HPTEC. Sin embargo, el diagnóstico definitivo y la caracterización hemodinámica requieren un cateterismo cardíaco derecho, considerado el estándar de oro. El manejo de la HP comienza con medidas generales, incluyendo actividad física supervisada y rehabilitación cardiopulmonar para pacientes estables. El tratamiento de soporte puede incluir diuréticos para la sobrecarga de volumen, oxigenoterapia para la hipoxemia y vacunación. El embarazo está asociado con un alto riesgo de mortalidad y generalmente se desaconseja en pacientes con HAP de riesgo intermedio o alto. El tratamiento farmacológico depende del grupo de HP. Para el Grupo 1 (HAP), la terapia se dirige a tres vías moleculares: la de la endotelina (antagonistas de receptores de endotelina como ambrisentán, macitentán), la del óxido nítrico (inhibidores de la PDE-5 como sildenafilo, o estimuladores de la guanilato ciclasa como riociguat) y la de la prostaciclina (análogos como epoprostenol, o agonistas como selexipag). La estratificación del riesgo es fundamental para guiar la terapia, y la combinación de fármacos desde el inicio es la estrategia recomendada para pacientes de riesgo intermedio o alto. Para los otros grupos, el tratamiento se centra en la causa subyacente. En el Grupo 2, se debe optimizar el manejo de la cardiopatía izquierda, ya que las terapias específicas para la HAP han demostrado ser perjudiciales. En el Grupo 3, el enfoque es tratar la enfermedad pulmonar de base y corregir la hipoxemia. Para el Grupo 4, el tratamiento de elección es la endarterectomía pulmonar (EAP) para trombos accesibles quirúrgicamente, mientras que el riociguat está indicado para pacientes no operables. La anticoagulación crónica es fundamental en este grupo.

BACKGROUND Wilson's disease (WD) is a rare metabolic disorder of copper accumulation in organs such as liver, brain, and cornea. Diagnoses and treatments are challenging in settings, where advanced diagnostic tests are unavailable, copper chelating agents are frequently scarce, healthcare professionals lack disease awareness, and medical follow-ups are limited. Prompt diagnoses and treatments help prevent complications, improve patients’ quality of life, and ensure a normal life expectancy. The clinical presentations and outcomes of WD can vary within a single family. CASE SUMMARY We present the cases of two siblings (19 and 27 years) from a consanguineous family in rural Ecuador, diagnosed as having WD during a family screening. The male patient, diagnosed at age 19 after his brother’s death from acute liver failure, presented with compensated cirrhosis, neurological symptoms, and bilateral Kayser-Fleischer rings. He developed progressive neurological deterioration during an irregular treatment with D-penicillamine due to medication shortages. His condition improved upon switching to trientine tetrahydrochloride, and his neurological symptoms improved over an 8-year period of follow-ups. The female patient, diagnosed at age 10, exhibited only biochemical alterations. Her treatment history was similar; however, she remained asymptomatic without disease progression over the same follow-up period. We discuss the potential influence of epigenetic mechanisms and modifier genes on the various phenotypes, emphasizing the need for research in these areas to optimize therapeutic strategies. CONCLUSION Our patients’ medical histories show how early diagnosis and treatment can prevent disease progression; and, how suboptimal treatments impact disease outcomes.

Hepatic cancer is a world health concern due to its high lethality. The main risk factor worldwide is having hepatic cirrhosis. The etiology of hepatic cirrhosis has changed in recent years, with metabolic-associated steatotic liver disease (MASLD) becoming the leading cause, displacing hepatitis C and B viruses and alcoholic liver disease. It is of the utmost importance to develop screening programs in at-risk populations for early detection. The survival rate of HCC, as determined by a group of specialists or an interdisciplinary committee, is a challenge we have taken on in a public health hospital in Ecuador. This retrospective study identified 71 patients diagnosed with hepatocellular carcinoma, mostly middle-aged men with a history of liver cirrhosis. No significant association was found between the presence of cirrhosis, laboratory abnormalities, and survival. However, the identification by imaging vascular invasion and extrahepatic extension were associated. This study highlights that patients with liver lesions identified through HCC screening have a higher survival rate over a one-year follow-up period.

Background: Hepatitis E virus (HEV) is a major cause of acute hepatitis worldwide, yet its impact in Latin America remains underexplored. Evidence suggests that chronic liver disease (CLD) patients infected with HEV face increased risks of disease progression and mortality. The PROGINS haplotype has been proposed to influence susceptibility to HEV. This study assessed HEV infection in CLD patients from Latin America and potential associated factors, including the PROGINS haplotype. Methods: A total of 971 individuals—784 with CLD and 187 healthy controls (HC)—from six countries (Argentina, Brazil, Chile, Colombia, Ecuador, and Peru) were analyzed for anti-HEV IgG and IgM (ELISA), HEV-RNA (RT-qPCR and nested PCR with Sanger sequencing and phylogenetic analysis), and the PROGINS haplotype (PCR). Results: The overall anti-HEV IgG seroprevalence was 15.2%: 15.4% in CLD and 14.4% in HC, with no statistical difference. Marked geographical disparities were observed, with Chile showing the highest (45.1%) and Argentina the lowest (4.2%) anti-HEV IgG detection rates. Cirrhosis and alcohol-related liver disease (ALD) were significantly associated with higher detection rates, while neither age nor sex influenced HEV seroprevalences. PROGINS haplotype showed no significant association with HEV infection. Anti-HEV IgM and HEV-RNA were detected in 11.2% and 0.4% of participants, respectively. Phylogenetic analysis confirmed zoonotic HEV-3 circulation in the region. Conclusions: This first multinational assessment of HEV in Latin America reveals heterogeneous seroprevalence across countries. Findings support considering HEV testing in diagnostic protocols for CLD patients particularly those with cirrhosis or ALD- when presenting with unexplained hepatic decompensation or acute hepatitis.