Caracterización clínico-epidemiológica de pacientes con enfermedad hepática esteatósica asociada a disfunción metabólica previa al trasplante en un hospital de cuarto nivel / Clinical-epidemiological characterization of patients with steatotic liver disease associated with metabolic dysfunction prior to transplantation in a fourth level hospital

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.

Experiencia de downstaging versus criterios de Milán para trasplante hepático por carcinoma hepatocelular en una cohorte prospectiva / Experience with downstaging versus Milan criteria for liver transplantation in patients with hepatocellular carcinoma in a prospective cohort

Introducción. El acceso al trasplante hepático (TH) en pacientes con carcinoma hepatocelular (CHC) se basa en la aplicación de criterios morfológicos rigurosos estipulados desde 1996, co-nocidos como criterios de Milán. Una de las estrategias descritas para expandir estos criterios se conoce como downstaging (reducción del estadiaje tumoral mediante terapias locorregionales). El objetivo de este estudio fue describir el comportamiento postrasplante de pacientes con CHC que ingresaron dentro de los parámetros de Milán, comparado con el de aquellos pacientes llevados a terapia de downstaging en un centro colombiano. Metodología. Se incluyeron pacientes adultos con cirrosis hepática (CH) y CHC que fueron llevados a TH en el Hospital Pablo Tobón Uribe, entre julio de 2012 a septiembre de 2021. Como desenlace principal se definió recurrencia y tiempo de recurrencia de la enfermedad tumoral, muerte por todas las causas y tiempo al fallecimiento. Se evaluaron las características sociodemográficas y clínicas de cada grupo. Se incluyeron scores pronósticos de recurrencia de la enfermedad tumoral. Resultados. Se trasplantaron 68 pacientes con CH y CHC, 50 (73,5 %) eran hombres y la edad promedio fue 59 años; 51 pacientes (75 %) cumplían con los criterios de Milán y 17 (25 %) fueron llevados a terapia de downstaging previo al TH. No hubo diferencias significativas en la supervivencia global y supervivencia libre de trasplante entre los dos grupos evaluados, p=0,479 y p=0,385, respectivamente. Tampoco hubo diferencia significativa en la recurrencia de la enfermedad tumoral entre ambos grupos (p=0,81). En total hubo 7 casos de recurrencia tumoral (10,2 %) y 11 casos de muerte (16,2 %). Conclusiones. No se encontraron diferencias significativas en recurrencia y mortalidad entre los pacientes que cumplían los criterios de Milán y los trasplantados luego de la terapia de downstaging, en un tiempo de se-guimiento de 53 meses hasta el último control posterior al trasplante hepático. Esta sería la primera evaluación prospectiva de un protocolo de downstaging para CHC en Colombia.

Introduction. Access to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is based on the application of rigorous morphological criteria stipulated since 1996, known as the Milan criteria. One of the strategies described to expand these criteria is known as downstaging (tu-mor staging reduction through locoregional therapies). The objective of this study was to describe the post-transplant performance of patients with HCC who were admitted within the Milan parameters, compared with those of patients taken to downstaging therapy, in a Colombian center. Methodolo-gy. Adult patients with cirrhosis and HCC that received LT between July 2012 and September 2021 at the Pablo Tobón Uribe Hospital were included. The main outcome was defined as recurrence and time to recurrence of the tumor disease, death from all causes, and time to death. The socio-demographic and clinical characteristics of each group were evaluated. Tumor disease recurrence prognostic scores were included. Results. Sixty-eight patients with cirrhosis and HCC received LT in the time frame, 50 (73.5%) were men and the mean age was 59 years. Fifty-one patients were trans-planted (75%) fulfilling Milan criteria, and 17 (25%) patients received downstaging therapies before LT. There were no significant differences in overall survival and transplant-free survival between the two groups, p=0.479 and p=0.385, respectively. There was also no significant difference in the recurrence of the tumor disease between both groups (p=0.81). In total there were 7 tumoral recurrences (10.2%) and 11 deaths (16.2%). Conclusions. There were no differences in recurrence and survival between patients transplanted fulfilling Milan criteria and those receiving downstaging therapies, following a mean time of 53 months after LT. This is the first prospective evaluation of the downstaging protocol in Colombia.

Hepatosplenic schistosomiasis-associated chronic portal vein thrombosis: risk factor for hepatocellular carcinoma? / Esquistossomose hepatosplênica associada à trombose crônica da veia porta: fator de risco para o carcinoma hepatocelular?

ABSTRACT BACKGROUND: Hepatosplenic schistosomiasis is an endemic disease prevalent in tropical countries and is associated with a high incidence of portal vein thrombosis. Inflammatory changes caused by both parasitic infection and portal thrombosis can lead to the development of chronic liver disease with potential carcinogenesis. AIMS: To assess the incidence of portal vein thrombosis and hepatocellular carcinoma in patients with schistosomiasis during long-term follow-up. METHODS: A retrospective study was conducted involving patients with schistosomiasis followed up at our institution between 1990 and 2021. RESULTS: A total of 126 patients with schistosomiasis were evaluated in the study. The mean follow-up time was 16 years (range 5-31). Of the total, 73 (57.9%) patients presented portal vein thrombosis during follow-up. Six (8.1%) of them were diagnosed with hepatocellular carcinoma, all with portal vein thrombosis diagnosed more than ten years before. CONCLUSIONS: The incidence of hepatocellular carcinoma in patients with schistosomiasis and chronic portal vein thrombosis highlights the importance of a systematic long-term follow-up in this group of patients.

RESUMO RACIONAL: A esquistossomose hepatoesplênica é uma doença endêmica prevalente em países tropicais e está associada a uma alta incidência de trombose da veia porta. Alterações inflamatórias causadas tanto pela infecção parasitária quanto pela trombose portal podem levar ao desenvolvimento de doença hepática crônica com potencial carcinogênico. OBJETIVOS: Avaliar a incidência de trombose da veia porta e carcinoma hepatocelular em pacientes com esquistossomose durante um seguimento de longo prazo. MÉTODOS: Foi realizado estudo retrospectivo envolvendo pacientes com esquistossomose acompanhados em nossa instituição entre 1990 e 2021. RESULTADOS: Um total de 126 pacientes com esquistossomose foram avaliados no estudo. O tempo médio de acompanhamento foi de 16 anos (variando de 5 a 31). Do total, 73 (57,9%) pacientes apresentaram trombose da veia porta durante o seguimento e seis (8,1%) deles foram diagnosticados com carcinoma hepatocelular, todos com trombose da veia porta diagnosticada há mais de 10 anos. CONCLUSÕES: A incidência de carcinoma hepatocelular em pacientes com esquistossomose e trombose da veia porta crônica destaca a importância de um acompanhamento sistemático de longo prazo nesse grupo de pacientes.

Hepatocellular carcinoma: A real-life experience in a specialized center in Bogotá, Colombia / Hepatocarcinoma: experiencia de la vida real en un centro especializado de Bogotá, Colombia

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most frequent malignant primary liver tumor globally. In 2018, it ranked sixth and represented the fourth cause of death from cancer; the five-year overall survival is 18 %. Most cases of HCC develop in patients with cirrhosis of any etiology, especially because of hepatitis B and C viruses, alcohol, and recently nonalcoholic steatohepatitis (NASH). Aim: To analyze the clinical characteristics, diagnostic methods, treatments, prognostic variables, and survival. Materials and methods: This retrospective descriptive study was conducted on a cohort of patients diagnosed with cirrhosis and treated between January 2011 and December 2020 at a health care center in Bogotá. The diagnosis of HCC was confirmed radiologically or by biopsy. We analyzed the information descriptively with absolute frequency measures in the case of categorical variables. For continuous variables, the information was summarized with measures of central tendency (mean or median) and their relevant measures of dispersion. Results: We included 152 patients diagnosed with HCC, with a mean age of 69.4 years; 51.3 % were men. The leading cause of HCC was nonalcoholic fatty liver disease (NAFLD), which accounted for almost a third of cases (32 %); other causes were alcohol (15 %) and hepatitis C virus (14 %). The median manifestation of the tumor was two nodules with a size close to 4 cm. Besides, 35 % of patients had a BCLC (Barcelona Clinic Liver Cancer) stage with curative options, and 25 % received curative treatment options. The first-line systemic therapy used in this cohort was sorafenib®, used in 35 patients (33.7 %). Survival curves showed that women, Child-Pugh class A, and BCLC stage 0 had higher median survival. Multivariate analysis showed a higher risk of death for males (hazard ratio [HR]: 2.16; confidence interval [CI]: 1.24-3.76), Child-Pugh class B (HR: 2.14; CI 1.16-3.95), and Child-Pugh class C (HR: 7.52; CI 2.88-19.57). Conclusions: NAFLD is the leading cause of HCC in this cohort. A third of patients are diagnosed in early BCLC stages with a curative treatment option, and 25 % are treated with curative therapies. Sorafenib was the first-line therapy in advanced HCC. Overall survival after diagnosis of HCC remains low, being necessary to join forces in the follow-up of patients with cirrhosis to improve these outcomes.

Resumen Introducción: el hepatocarcinoma (HCC) es el tumor hepático primario maligno más frecuente en el mundo: en 2018 ocupó la sexta posición y representó la cuarta causa de muerte por cáncer; la supervivencia global a 5 años es del 18 %. La mayoría de los casos de HCC se desarrolla en pacientes con cirrosis de cualquier etiología, especialmente por virus de la hepatitis B y C, alcohol y, recientemente, por la esteatohepatitis no alcohólica (NASH). Objetivo: analizar las características clínicas, métodos de diagnóstico, tratamientos, variables pronósticas y supervivencia. Metodología: estudio descriptivo retrospectivo de una cohorte de pacientes con diagnóstico de cirrosis atendidos entre enero de 2011 y diciembre de 2020 en un centro de atención médica de Bogotá, con diagnóstico de HCC confirmado radiológicamente o por biopsia. La información se analizó de forma descriptiva con medidas de frecuencia absoluta en el caso de las variables categóricas; para las variables continuas se resumió la información con medidas de tendencia central (media o medianas) y su respectiva medida de dispersión. Resultados: se incluyeron 152 pacientes diagnosticados con HCC, con edad promedio de 69,4 años, 51,3 % eran hombres. La principal causa de HCC fue el hígado graso no alcohólico (NAFLD), que representó casi una tercera parte de los casos (32 %); otras causas fueron el alcohol (15 %) y el virus de la hepatitis C (14 %). La mediana de presentación del tumor fue de 2 nódulos con un tamaño cercano a 4 cm. El 35 % de los pacientes tenía un estadio BCLC (Barcelona Clinic Liver Cancer) con opciones curativas y el 25 % de los pacientes recibió opciones curativas de tratamiento. La terapia sistémica de primera línea utilizada en esta cohorte fue el sorafenib®, que se utilizó en 35 pacientes (33,7 %). Las curvas de supervivencia mostraron que las mujeres, el estadio Child-Pugh A y el estadio BCLC 0 presentaron mayores medianas de supervivencia. El análisis multivariado evidenció un mayor riesgo de muerte al ser hombre (Hazard ratio [HR]: 2,16; intervalo de confianza [IC]: 1,24 a 3,76), estar en los estadios Child-Pugh B (HR: 2,14; IC: 1,16 a 3,95) y Child-Pugh C (HR: 7,52; IC: 2,88 a 19,57). Conclusiones: el NAFLD es la principal causa de HCC en la presente cohorte, una tercera parte de los pacientes se diagnostica en estadios BCLC tempranos con opción curativa de tratamiento, y un 25 % se trata con terapias curativas. El sorafenib fue la terapia de primera línea en HCC avanzado. La supervivencia global luego del diagnóstico de HCC sigue siendo baja, y es necesario aunar esfuerzos en el seguimiento de los pacientes con cirrosis para mejorar estos resultados.

Pacientes com carcinoma hepatocelular são favorecidos no atual sistema brasileiro de alocação de fígados para transplante. Análise de riscos competitivos / Hepatocellular carcinoma patients are advantaged in the current brazilian liver transplant allocation system. a competing risk analysis

ABSTRACT BACKGROUND: In Brazil, the Model for End-Stage Liver Disease (MELD) score is used to prioritize patients for deceased donor liver transplantation (DDLT). Patients with hepatocellular carcinoma (HCC) receive standardized MELD exception points to account for their cancer risk of mortality, which is not reflected by their MELD score. OBJECTIVE: To compare DDLT rates between patients with and without HCC in Rio Grande do Sul, the Southernmost state of Brazil. METHODS - We retrospectively studied 825 patients on the liver-transplant waiting list from January 1, 2007, to December 31, 2016, in a transplant center located in Porto Alegre, the capital of Rio Grande do Sul, to compare DDLT rates between those with and without HCC. The time-varying hazard of waiting list/DDLT was estimated, reporting the subhazard ratio (SHR) of waiting list/DDLT/dropout with 95% confidence intervals (CI). The final competing risk model was adjusted for age, MELD score, exception points, and ABO group. RESULTS: Patients with HCC underwent a transplant almost three times faster than patients with a calculated MELD score (SHR 2.64; 95% CI 2.10-3.31; P<0.001). The DDLT rate per 100 person-months was 11.86 for HCC patients vs 3.38 for non-HCC patients. The median time on the waiting list was 5.6 months for patients with HCC and 25 months for patients without HCC. CONCLUSION: Our results demonstrated that, in our center, patients on the waiting list with HCC have a clear advantage over candidates listed with a calculated MELD score.

RESUMO CONTEXTO: No Brasil, o escore MELD (Model for End-Stage Liver Disease) é utilizado para priorizar os pacientes para transplante hepático de doador falecido (THDF). Pacientes com carcinoma hepatocelular (CHC) recebem pontos de exceção padronizados pelo MELD para contrapesar o risco de mortalidade do seu câncer, que não é refletido pelo seu escore MELD. OBJETIVO: Comparar as taxas de THDF entre pacientes com e sem CHC no Rio Grande do Sul, o Estado mais ao sul do Brasil. MÉTODOS: Foram estudados retrospectivamente 825 pacientes em lista de espera de transplante de fígado entre 1 de janeiro de 2007 e 31 de dezembro de 2016 em um centro de transplantes localizado em Porto Alegre, capital do Rio Grande do Sul, para comparação das taxas de THDF entre aqueles com e sem CHC. Foi estimado o risco variável no tempo de lista de espera/THDF, com relato da taxa de sub-risco (SHR) de lista de espera/THDF/desistência com intervalos de confiança (IC) de 95%. O modelo final de risco competitivo foi ajustado para idade, escore MELD, pontos de exceção e grupo ABO. RESULTADOS: Os candidatos com CHC foram submetidos a um transplante quase três vezes mais rápido do que os pacientes com um escore MELD calculado (SHR 2,64; IC 95% 2,10-3,31; P<0,001). A taxa de THDF por 100 pessoas-mês foi de 11,86 para os pacientes com CHC vs 3,38 para os pacientes sem CHC. O tempo mediano de permanência em lista de espera foi de 5,6 meses para os pacientes com CHC e 25 meses para os pacientes sem CHC. CONCLUSÃO: Nossos resultados demonstraram que, em nosso centro, pacientes em lista de espera com CHC têm evidente vantagem sobre candidatos listados com um escore MELD calculado.

Surgical management of large hepatocellular carcinoma: the first single-center study from western india / Manejo cirúrgico de grandes carcinomas hepatocelulares: primeiro estudo de um único centro da índia ocidental

ABSTRACT Background: Majority of patients with large size HCC (>10 cm) are not offered surgery as per Barcelona Clinic Liver Cancer (BCLC) criteria and hence, their outcomes are not well studied, especially from India, owing to a lower incidence. Aim: To analyze outcomes of surgery for large HCCs. Methods: This retrospective observational study included all patients who underwent surgery for large HCC from January 2007 to December 2017. The entire perioperative and follow up data was collected and analyzed. Results: Nineteen patients were included. Ten were non-cirrhotic; 16 were BCLC grade A; one BCLC grade B; and two were BCLC C. Two cirrhotic and three non-cirrhotic underwent preoperative sequential trans-arterial chemoembolization and portal vein embolization. Right hepatectomy was the most commonly done procedure. The postoperative 30-day mortality rate was 5% (1/19). Wound infection and postoperative ascites was seen in seven patients each. Postoperative liver failure was seen in five. Two cirrhotic and two non-cirrhotic patients had postoperative bile leak. The hospital stay was 11.9±5.4 days (median 12 days). Vascular invasion was present in four cirrhotic and five non-cirrhotic patients. The median follow-up was 32 months. Five patients died in the follow-up period. Seven had recurrence and median recurrence free survival was 18 months. The cumulative recurrence free survival was 88% and 54%, whereas the cumulative overall survival was 94% and 73% at one and three years respectively. Both were better in non-cirrhotic; however, the difference was not statistically significant. The recurrence free survival was better in patients without vascular invasion and the difference was statistically significant (p=0.011). Conclusion: Large HCC is not a contraindication for surgery. Vascular invasion if present, adversely affects survival. Proper case selection can provide the most favorable survival with minimal morbidity.

RESUMO Racional: A maioria dos pacientes com CHC de grande porte (>10 cm) não tem indicação cirúrgica conforme os critérios do Barcelona Clinic Liver Cancer (BCLC) e, portanto, seus resultados não são bem estudados, principalmente na Índia, devido a uma menor incidência. Objetivo: Analisar os resultados da cirurgia para HCCs de grande porte. Métodos: Este estudo observacional retrospectivo incluiu todos os pacientes submetidos à cirurgia para grandes CHC de janeiro de 2007 a dezembro de 2017. Todos os dados perioperatórios e de acompanhamento foram coletados e analisados. Resultados: Dezenove pacientes foram incluídos. Dez não eram cirróticos; 16 eram BCLC grau A; um BCLC grau B; e dois eram BCLC C. Dois cirróticos e três não-cirróticos foram submetidos à quimioembolização transarterial sequencial pré-operatória e embolização da veia porta. Hepatectomia direita foi o procedimento mais comumente realizado. A taxa de mortalidade pós-operatória em 30 dias foi de 5% (1/19). Infecção da ferida e ascite pós-operatória foram observadas em sete pacientes cada. Insuficiência hepática pós-operatória foi observada em cinco. Dois pacientes cirróticos e dois não cirróticos apresentaram vazamento de bile no pós-operatório. O tempo de internação foi de 11,9±5,4 dias (mediana de 12 dias). A invasão vascular estava presente em quatro pacientes cirróticos e cinco não cirróticos. O acompanhamento médio foi de 32 meses. Cinco pacientes morreram no período de acompanhamento. Sete tiveram recorrência e sobrevida mediana livre de recorrência foi de 18 meses. A sobrevida livre de recorrência cumulativa foi de 88% e 54%, enquanto a sobrevida global cumulativa foi de 94% e 73% em um e três anos, respectivamente. Ambos eram melhores em não-cirróticos; no entanto, a diferença não foi estatisticamente significante. A sobrevida livre de recidiva foi melhor nos pacientes sem invasão vascular e a diferença foi estatisticamente significante (p=0,011). Conclusão: CHC grande não é contraindicação para cirurgia. Invasão vascular, se presente, afeta adversamente a sobrevida. Seleção adequada de casos pode fornecer sobrevida mais favorável com morbidade mínima.

Retrospective analysis of efficacy, safety, and prognostic factors in a cohort of Chinese hepatocellular carcinoma patients treated with drug-eluting bead transarterial chemoembolization

The aim of our study was to assess the efficacy, safety, and prognostic factors of drug-eluting bead transarterial chemoembolization (DEB-TACE) in Chinese hepatocellular carcinoma (HCC) patients. Patients (n=102) diagnosed as primary HCC were consecutively enrolled in this retrospective cohort study. Treatment responses were assessed following the modified Response Evaluation Criteria in Solid Tumors. Progression-free survival (PFS) and overall survival (OS) were evaluated, and adverse events (AEs) as well as liver function-related laboratory indexes of all DEB-TACE records (N=131) were assessed. Complete response (CR) rate, objective response rate, and disease control rate were 51.0, 87.3, and 95.1%, respectively, at 1-3 months post DEB-TACE. The mean PFS and OS were 227 (95%CI: 200-255) days and 343 (95%CI: 309-377) days, respectively. Multivariate logistic regression revealed that portal vein invasion and abnormal total protein (TP) were independent predictive factors for worse CR, and multivariate Cox's regression analysis showed that multifocal disease independently correlated with shorter PFS. Most of the liver function-related laboratory indexes worsened at 1 week but recovered at 1-3 months post-treatment, only the percentage of patients with abnormal ALP increased at 1-3 months. In addition, 112 (85.5%), 84 (64.1%), 53 (40.5%), 40 (30.5%), and 16 (12.2%) patients had pain, fever, nausea, vomiting, and other AEs, respectively. DEB-TACE is efficient and safe in Chinese HCC patients, and portal vein invasion, abnormal TP level as well as multifocal disease could be used as unfavorable prognostic factors to DEB-TACE treatment.

HPA-1a/1b could be considered a molecular predictor of poor prognosis in chronic hepatitis C

Abstract INTRODUCTION: HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS: PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS: There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS: The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.

Schistosomal liver fibrosis and hepatocellular carcinoma - case series of patients submitted to liver transplantation

ABSTRACT Schistosomiasis affects approximately 207 million people in 76 countries. The association between hepatocellular carcinoma and Schistosoma mansoni infection has been investigated. Studies using animal models suggest that the parasite may accelerate the oncogenic process when combined with other factors, such as hepatitis C virus infection or exposure to a carcinogen. Herein, we report a case series of six hepatocellular carcinoma patients from Northeast Brazil, with negative serology for both hepatitis B and C virus, submitted to liver transplantation, whose explant showed evidence of schistosomal liver fibrosis. Since all patients enrolled in this study were submitted to liver transplantation, we were able to access the whole explanted liver and perform histopathological analysis, which is often not possible in other situations. Although 50% of them showed signs of liver failure, no cirrhosis or any liver disease other than schistosomal fibrosis had been detected. These uncommon findings suggest that Schistosoma mansoni infection might predispose to hepatocellular carcinoma development, regardless of the absence of other risk factors.

Negative serology of Fasciola hepatica infection in patients with liver cancer in Peru: a preliminary report

Abstract INTRODUCTION: The etiology of several hepatocellular carcinoma (HCC) cases remains largely unknown. Although Fasciola hepatica has been associated with liver fibrosis in Latin America, it has not yet been associated with HCC. This study aimed to determine the existence of specific IgG antibodies against F. hepatica in the serum samples of HCC patients. METHODS In total, 13 serum samples from 13 HCC patients were screened using Fas2-ELISA. RESULTS Fas2-ELISA demonstrated negative results in all HCC patients included in this study. CONCLUSIONS The pre-existence of F. hepatica infection in HCC patients needs to be further investigated in epidemiological and experimental studies.

Hemoperitoneo como manifestación inicial de carcinoma hepatocelular: reporte de tres casos / Hemoperitoneum as initial manifestation of hepatocellular carcinoma: report of three cases

Hepatocellular carcinoma (HCC) is the main primary liver malignancy. Its prevalence is increasing and is associated in 90% to cirrhotic patients. Hemoperitoneum secondary to spontaneous rupture of the tumor is an uncommon complication in Latin America and the Western world, being more prevalent in Asian races. However, it is associated to hemodynamic repercussion with high mortality, therefore high level of suspicion and early treatment are required. Regarding the management of the condition, in addition to hemodynamic stabilization, active hemostatic control is recommended over conservative management, transarterial chemoembolization being currently the chosen alternative. We present a series of three clinical cases of patients who debuted with clinical manifestation of hemoperitoneum during the diagnostic process of a HCC.

El carcinoma hepatocelular (CHC) corresponde a la principal neoplasia maligna primaria hepática. Su prevalencia va en aumento y se asocia en 90% a pacientes cirróticos. El hemoperitoneo secundario a rotura espontánea del tumor constituye una complicación infrecuente en Latinoamérica y Occidente, siendo más prevalente en razas asiáticas. Sin embargo, se asocia a repercusión hemodinámica con alta mortalidad, por lo que requiere un alto índice de sospecha y tratamiento oportuno precoz. En cuanto al manejo del cuadro, junto a la estabilización hemodinámica se recomienda un control hemostático activo por sobre manejo conservador, siendo la embolización transarterial la alternativa de elección actualmente. Describimos a continuación una serie de tres casos clínicos de pacientes que debutan con manifestación clínica de hemoperitoneo durante el proceso diagnóstico de un CHC.

Adherence to BCLC recommendations for the treatment of hepatocellular carcinoma: impact on survival according to stage

OBJECTIVES: This study sought to assess the adherence of newly diagnosed hepatocellular carcinoma patients to the Barcelona Clinic Liver Cancer system treatment guidelines and to examine the impact of adherence on the survival of patients in different stages of the disease. METHODS: This study included all patients referred for the treatment of hepatocellular carcinoma between 2010 and 2012. Patients (n=364) were classified according to the Barcelona Clinic Liver Cancer guidelines. Deviations from the recommended guidelines were discussed, and treatment was determined by a multidisciplinary team. The overall survival curves were estimated with the Kaplan-Meier method and were compared using the log-rank test. RESULTS: The overall rate of adherence to the guidelines was 52%. The rate of adherence of patients in each scoring group varied as follows: stage 0, 33%; stage A, 45%; stage B, 78%; stage C, 35%; and stage D, 67%. In stage 0/A, adherent patients had a significantly better overall survival than non-adherent patients (hazard ratio=0.19, 95% confidence interval (CI): 0.09-0.42; p<0.001). Among the stage D patients, the overall survival rate was worse in adherent patients than in non-adherent patients (hazard ratio=4.0, 95% CI: 1.67-9.88; p<0.001), whereas no differences were observed in patients in stages B or C. CONCLUSIONS: The rate of adherence to the Barcelona Clinic Liver Cancer staging system in clinical practice varies according to clinical disease stage. Adherence to the recommended guidelines positively impacts survival, especially in patients with early-stage disease.

Retrospective analysis of hepatitis B virus chronic infection in 247 patients: clinical stages, response to treatment and poor prognostic factors

Abstract Background: Chronic hepatitis B is a major cause of cirrhosis, and the natural history of the disease has several clinical stages that should be thoroughly understood for the implementation of proper treatment. Nonetheless, curing the disease with antiviral treatment remains a challenge. Aims: To describe the clinical course, response to treatment, and poor prognostic factors in 247 hepatitis B virus chronic infection patients treated in a tertiary hospital in Brazil. Methods: This was a retrospective and observational study, by analyzing the medical records of HBV infected patients between January 2000 and January 2015. Results: Most patients were male (67.2%) and 74.1% were HBeAg negative. Approximately 41% had cirrhosis and 8.5% were hepatitis C virus coinfected. The viral load was negative after two years on lamivudine, entecavir and tenofovir in 86%, 90.6%, and 92.9% of the patients, respectively. The five-year resistance rates for lamivudine, adefovir, entecavir, and tenofovir were 57.5%, 51.8%, 1.9%, and 0%, respectively. The overall seroconversion rates were 31.2% for HBeAg and 9.4% for HBsAg. Hepatocellular carcinoma was diagnosed in 9.7% of patients, liver transplantation was performed in 9.7%, and overall mortality was 10.5%. Elevations of serum alanine aminotransferase (p = 0.0059) and viral load (p < 0.0001) were associated with progression to liver cirrhosis. High viral load was associated with progression to hepatocellular carcinoma (p < 0.0001). Significant risk factors associated with death were elevated alanine aminotransferase (p = 0.0039), liver cirrhosis (p < 0.0001), high viral load (p = 0.007), and hepatocellular carcinoma (p = 0.0008). HBeAg positive status was not associated with worse outcomes, and treatment may have been largely responsible. Conclusions: Elevations of viral load and serum alanine aminotransferase may select patients with worse prognosis, especially progression to cirrhosis and hepatocellular carcinoma, which were strongly association with death.

Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B

Abstract INTRODUCTION Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC. METHODS: A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB. RESULTS: Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression. CONCLUSIONS: We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.

Metastatic Lymphoepithelioma-like Hepatocellular Carcinoma: a Potential Diagnostic Pitfall and Demonstration of Pd-l1 Expression

Abstract: Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare primary hepatic neoplasm with female predominance and relatively good prognosis. We report a 73-year-old female with chronic hepatitis B who developed metastatic lesions 5 years after underwent resection for LEL-HCC. The metastatic lesions showed a spectrum of morphologic findings, which could be mistaken for other entities such as lymphoma, particularly in lesions with single-cell infiltrative pattern and abundant tumor-infiltrating lymphocytes. Immunohistochemical study to confirm the origin of the neoplastic cells is important to make the diagnosis. We also highlighted the clinicopathologic correlation and potential therapeutic implication of programmed death ligand-1 expression in LEL-HCC.

Is resection of hepatocellular carcinoma in the era of liver transplantation worthwile? A single center experience / Ressecção de carcinoma hepatocelular na era do transplante de fígado: vale a pena? Experiência de um único centro

ABSTRACT Background - Liver resection for hepatocellular carcinoma is a potentially curative therapeutic procedure that can be performed readily after its indication, without the need of a long waiting time and lower costs when compared to liver transplantation, being a good alternative in patients with preserved/good liver function. Objective - Evaluate long-term results of liver resection from a high volume single center for selected patients with hepatocellular carcinoma in a context of a long waiting list for liver transplant. Methods - One hundred and one patients with hepatocellular carcinoma, with a mean age of 63.1 years, and preserved liver function were submitted to liver resection. Clinical and pathological data were evaluated as prognostic factors. Mean follow-up was 39.3 months. Results - All patients had a single nodule and 57 (58.2%) patients were within the Milan criteria. The size of the nodule ranged from 1 to 24 cm in diameter. In 74 patients, liver resection was performed with the open approach and in 27 (26.7%) was done laparoscopically. Postoperative morbidity was 55.3% being 75.5% of the complications classified as Dindo-Clavien I and II and operative mortality was 6.9%. Five-year overall and disease free survival rates were 49.9% and 40.7%, respectively.After a log-rank univariate analysis, the levels of preoperative alpha-fetoprotein (P=0.043), CA19-9 (P=0.028), capsule invasion (P=0.03), positive margin (R1-R2) (P=0.004) and Dindo-Claviens' morbidity classification IV (P=0.001) were the only parameters that had a significant negative impact on overall survival. On the odds-ratio evaluation, the only significant factors for survival were high levels of alpha-fetoprotein (P=0.037), and absence of free margins (P=0.008). Conclusion - Resection, for selected cases, is a potentially curative treatment with acceptable morbidity and mortality and, in a context of a long waiting list for transplant, plays an important role for the treatment of hepatocellular carcinoma.

RESUMO Contexto - A ressecção do carcinoma hepatocelular é um procedimento terapêutico potencialmente curativo que pode ser realizado imediatamente após sua indicação, sem a necessidade de longo tempo de espera e com custos mais baixos quando comparado com o transplante hepático, sendo uma boa alternativa em pacientes com função hepática preservada. Objetivo - Avaliar os resultados a longo prazo da ressecção hepática em centro de alto volume cirúrgico para pacientes selecionados com carcinoma hepatocelular em um contexto de uma longa lista de espera para transplante de fígado. Métodos - Cento e um pacientes com carcinoma hepatocelular, com idade média de 63,1 anos, e função hepática preservada foram submetidos à ressecção hepática. Os dados clínicos e patológicos foram avaliados como fatores prognósticos. O seguimento médio foi de 39,3 meses. Resultados - Todos os pacientes apresentavam um único nódulo e 57 (58,2%) estavam dentro dos critérios de Milão. O tamanho do nódulo variou de 1 a 24 cm de diâmetro. Em 74 pacientes, a ressecção hepática foi realizada com a abordagem aberta e em 27 (26,7%) através de laparoscopia.A morbidade pós-operatória foi de 55,3%, sendo 75,5% das complicações classificadas como Dindo-Clavien I e II e a mortalidade operatória foi de 6,9%. As sobrevida global e livre de doença em 5 anos foram 49,9% e 40,7%, respectivamente. Depois de análise univariada log-rank, os níveis de alfa-fetoproteína no pré-operatório (P=0,043), CA19-9 (P=0,028), invasão de cápsula (P=0,03), margem positiva (R1-R2) (P=0,004) e classificação de morbidade de Dindo-Claviens tipo IV (P=0,001) foram os únicos parâmetros que tiveram um impacto negativo significativo na sobrevida global. Na avaliação de risco relativo (odds-ratio), os únicos fatores importantes para a sobrevivência foram altos níveis de alfa-fetoproteína (P=0,037), e ausência de margens livres (P=0,008). Conclusão - A ressecção hepática em casos seleccionados, é um tratamento potencialmente curativo com morbilidade e mortalidade aceitáveis e, num contexto de uma longa lista de espera para transplante, tem um papel importante para o tratamento do carcinoma hepatocelular.

Análise retrospectiva da infecção crônica pelo vírus da hepatite B em 247 pacientes: fases evolutivas, resposta ao tratamento e fatores de pior prognóstico / Retrospective analysis of hepatitis B virus chronic infection in 247 patients clinical stages, response to treatment and poor prognostic factors

Introdução. A hepatite B crônica é uma importante causa de cirrose hepática e a história natural da doença tem várias fases clínicas que devem ser bem entendidas para se realizar o tratamento adequado. Objetivos. Descrever o comportamento clínico, a resposta ao tratamento e os fatores de pior prognóstico em 247 pacientes com infecção crônica pelo vírus da hepatite B. Métodos. Estudo retrospectivo observacional, realizado através da análise dos prontuários dos pacientes entre janeiro de 2000 e janeiro de 2015. Resultados. A maioria dos pacientes eram do gênero masculino (67,2%) e 74,1% eram HBeAg negativo. Cerca de 41% tinham cirrose hepática e 8,5% eram coinfectados pelo vírus da hepatite C. A negativação da carga viral em um ano com lamivudina, entecavir e tenofovir foi respectivamente de 56%, 75% e 75%; efeitos adversos foram mais comuns com tenofovir. A resistência virológica em cinco anos a lamivudina, adefovir e entecavir foi respectivamente de 57,5%, 51,8% e 1,9%. A taxa geral de soroconversão do HBeAg foi de 31,2% e do HBsAg foi de 9,7%. Carcinoma hepatocelular foi diagnosticado em 9,7%, transplante hepático foi realizado em 9,7% e a mortalidade geral foi de 10,5%. Elevações de alanina aminotransferase (p=0,0194) e carga viral (p<0,0001) foram associadas à evolução para cirrose hepática. Carga viral elevada foi associada à evolução para carcinoma hepatocelular (p=0,0019). Os fatores de risco significativos relacionados ao óbito foram elevação de alanina aminotransferase (p=0,0118), cirrose hepática (p<0,0001) e carcinoma hepatocelular (p=0,0008). Positividade para o HBeAg não foi associada a piores desfechos. Conclusões. Cirrose hepática e carcinoma hepatocelular foram associados a um pior prognóstico e novos estudos devem ser direcionados para prevenir estes fatores com a finalidade de diminuir o óbito relacionado a esse vírus. (AU)

Background. Chronic hepatitis B is a major cause of cirrhosis, and the natural history of the disease has several clinical stages that should be thoroughly understood for the implementation of proper treatment. Aim. To describe the clinical course, response to treatment and poor prognostic factors in 247 hepatitis B virus chronic infection patients. Methods. We carried out a retrospective and observational study, by analyzing the medical records of patients between January 2000 and January 2015. Results. Most patients were male (67.2%) and 74.1% were HBeAg negative. Approximately 41% had liver cirrhosis and 8.5% were hepatitis C virus coinfected. The viral load was negative in one year with lamivudine, entecavir and tenofovir in 56%, 75% and 75% of patients, respectively; adverse effects were more frequent with tenofovir. Virological resistance in five years for lamivudine, adefovir and entecavir was 57.5%, 51.8% and 1.9%, respectively. The overall rate of seroconversion was 31.2% for HBeAg and 9.7% for HBsAg. Hepatocellular carcinoma was diagnosed in 9.7% of patients, liver transplantation was performed in 9.7% and overall mortality was 10.5%. Elevations of serum alanine aminotransferase (p = 0.0194) and viral load (p <0.0001) were associated with progression to liver cirrhosis. High viral load was associated with progression to hepatocellular carcinoma (p = 0.0019). Significant risk factors associated with death were elevated alanine aminotransferase (p = 0.0118), liver cirrhosis (p <0.0001) and hepatocellular carcinoma (p = 0.0008). HBeAg positive state was not associated with worse outcomes. Conclusions. Liver cirrhosis and hepatocellular carcinoma were associated with a worse prognosis and further studies should concentrate on prevention of these factors in order to reduce mortality.(AU)

Socioeconomic disparities in access to a hepatocellular carcinoma screening program in Brazil

OBJECTIVES: Cirrhotic patients must receive an abdominal ultrasound every 6 months as part of hepatocellular carcinoma (HCC) screening. The aim of this study was to assess if HCC screening was performed as recommended by the literature and to observe the differences between the private and public services in Brazil. METHODS: We analyzed data from the HCC screenings of 253 cirrhotic patients from the University Hospital (n=177) and private sector (n=76) in Vitória, ES, Brazil. RESULTS: Ultrasound screening was performed every 13.1 months on average (SD 9.02). In 37 out of 253 patients, the screenings were performed close to the recommended frequency; 16 were performed every 6 months, and 21 were mostly performed during the follow-up period every 6 months. In the remaining 216 cases, ultrasounds were not performed according to the guidelines; for 106 patients, less than 50% of all ultrasounds were performed every 6 months and 110 patients showed an interval greater than one year. Patients from the private sector received ultrasound screenings near the ideal in 28.9% of cases, while patients from the University Hospital received ultrasounds in only 8.4% of cases (p<0.0001). HCC was diagnosed in 30 patients (11.8%). For these 30 patients, 11 screenings were properly performed within 6 months (36.6%) and only 1 out of the 11 (9%) met the criteria for transplant. In the remaining 19 patients who did not receive the screening within 6 months, 6 (31.5%) did not meet the criteria for transplant. CONCLUSION: HCC screening in our environment was irregularly performed, mainly in the public service setting, which prevented early diagnosis in a large number of patients.

Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases’ 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul). The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and without cirrhosis in Brazil. In this survey, hepatocellular carcinoma was observed in elevated numbers of patients with steatohepatitis without cirrhosis.