Role of metformin in the diagnosis, prevention, and treatment of hepatocellular carcinoma / 中南大学学报(医学版)

Hepatocellular carcinoma is one of the most common malignant tumors in the world. Although there are many options for the treatment of hepatocellular carcinoma, such as surgical resection, interventional therapy, radiotherapy, chemotherapy, targeted therapy and liver transplantation, the poor therapeutic effect seriously reduces the quality of life for patients and also increases the social and economic burden. Metformin is originally used as the first-line drug for type 2 diabetes, but it has been found to play a certain effect in the prevention and treatment of malignant tumor. The potential roles of metformin against hepatocellular carcinoma, such as regulation of the microenvironment, proliferation signal pathway, metabolism, invasion and metastasis, apoptosis, autophagy, and epigenetics of hepatoma cells. It provides a new choice for the prevention and treatment of hepatocellular carcinoma.

Consensus on secondary prevention of primary liver cancer (2021 version) / 中华肝脏病杂志

In order to standardize the effective prevention, early screening and diagnosis of the population at risk of primary liver cancer, the Chinese Society of Hepatology and Chinese Medical Association organized the relevant domestic experts to formulate the "Consensus on Secondary Prevention of Primary Liver Cancer (2021 version)," based on the basic, clinical and preventive research progress, combined with the actual situation at home and abroad, so as to provide an important basis for the prevention, screening and early diagnosis of primary liver cancer in the population of chronic liver disease.

Caracterização do efeito anti-neoplásico do butirato em duas linhagens celulares de rato derivadas de tumores hepáticos com diferente ní­vel de diferenciação / Characterization of the anti-neoplastic effect of butyrate in two mouse cell lines derived from hepatic tumors with different levels of differentiation

O carcinoma hepatocelular (HCC) é uma neoplasia primária com mau prognóstico e alta taxa de recorrência. Estudos recentes demostram que o HCC pode ser classificado em três subtipos segundo o perfil molecular. Destes subtipos, o HCC pouco diferenciado apresenta pior prognostico. Neste sentido, torna-se de particular interesse o estudo de compostos com efeitos diferenciadores e citotóxicos nas células destas neoplasias pouco diferenciadas. O butirato, um ácido graxo de cadeia curta produzido pela fermentação microbiana da fibra alimentar no intestino, tem demonstrado atividade anti-neoplásica e capacidade moduladora da diferenciação celular em diversos tipos celulares, incluindo linhagens de HCC humano e células progenitoras hepáticas. Assim, objetivou-se neste estudo, caracterizar o efeito do butirato de sódio (NaBu) em duas linhagens de células neoplásicas de rato: uma pouco diferenciada (GP7TB) e a outra, uma linhagem derivada de um HCC diferenciado (JM-1). A linhagem GP7TB mostrou maior resistência ao NaBu (ED50= 7,7 mM) do que as células JM-1 (ED50= 5,2 mM). A redução na viabilidade celular após 72 h de tratamento com NaBu esteve relacionada com a diminuição na proliferação celular e no caso das células GP7TB, de um aumento na apoptose. O tratamento com NaBu induziu alterações morfológicas nas duas linhagens celulares, porém apenas nas células do tipo GP7TB, essas alterações sugerem um processo de diferenciação/transdiferenciação celular. O aumento na expressão de genes envolvidos no controle da pluripotência de células tronco, assim como de alguns marcadores de células tronco, sugere que o NaBu induziu uma reprogramação profunda das células GP7TB. Por outro lado, a redução na expressão de genes relacionados com migração e plasticidade celular assim como de proliferação celular apontam que estas células diminuíram seu potencial invasivo e a capacidade de autorenovação. Embora sejam necessárias análises adicionais para confirmar o efeito observado nos perfis de expressão gênica, os resultados deste estudo sugerem que o NaBu apresenta efeito antineoplásico por meio da redução da proliferação, aumento da apoptose e modulação da expressão de genes associados com a transição epitéliomesenquimal em células com características tronco tumorais

Hepatocellular carcinoma (HCC) is a primary neoplasia with poor prognosis and high recurrence rate. Recent evidence suggests that HCC can be classified in three different subtypes based on their molecular profile. Among these subtypes, the poorlydifferentiated HCC has the worst prognosis. Therefore, the study of compounds with pro-differentiating and cytotoxic effects on poorly-differentiated neoplastic cells represents a matter of primary concern. Butyrate which is a short-chain fatty acid produced by microbial fermentation in the intestine, has demonstrated anti-neoplastic activity and pro-differentiating potential in several cell types, including, human HCC cell lines and liver progenitor cells. In this study, we aimed to characterize the effect of sodium butyrate (NaBu) on two neoplastic cell lines derived from rats: a poorlydifferentiated cell line (GP7TB) and, a cell line derived from a well-differentiated HCC. GP7TB showed increased resistance to NaBu treatment (ED50= 7.7 mM) compared to JM-1 (ED50= 5.2 mM). The reduction in cell viability observed after 72 h of treatment was explained by a reduction in cell proliferation and, in the case of GP7TB, by increased levels of apoptosis. The NaBu treatment induced morphological alterations in both cell lines. However, only in the case of GP7TB cells, the alterations suggested a differentiation/transdifferentiation process. The up-regulation of genes involved in pluripotency and genes expressing stem cell markers indicated that NaBu triggered a deep reprogramming of GP7TB cells. Besides, a down-regulation in the expression of genes related with cell migration and plasticity suggested that these cells reduced their invasive potential and their self-renewal capacity. Additional analyses are necessary to confirm the observed effect on gene expression profiles. However, the results of this study suggest that NaBu exert anti-neoplastic effects through apoptosis, reduction of cell proliferation and downregulation of genes associated with epithelial-mesenchymal transition of cancer stem-like cells

Lipídios estruturados obtidos por interesterificação da tributirina com óleo de linhaça e seu potencial quimiopreventivo durante a fase de promoção inicial da hepatocarcinogênese experimental em ratos / Structured lipids obtained from intersterification of tributyrin and flax seed oil and their chemopreventive potential during early promotion phase of experimental hepatocarcinogenesis in rats

A combinação de agentes quimiopreventivos com diferentes mecanismos de ação tem sido considerada uma estratégia promissora para a prevenção do câncer. Dentre os diversos compostos bioativos em alimentos, destacam-se a tributirina, um pró-fármaco do ácido butírico presente em laticínios e produzido pela fermentação de fibras dietéticas, e o óleo de linhaça, fonte de ácido alfa linolênico. Nesse contexto, foi avaliada a atividade quimiopreventiva de lipídios estruturados obtidos a partir da interesterificação enzimática de tributirina e óleo de linhaça durante a fase de promoção inicial da hepatocarcinogênese experimental. Ratos Wistar machos submetidos ao modelo do hepatócito resistente receberam diariamente, por via intragástrica (i.g), maltodextrina, óleo de linhaça, tributirina, a mistura não esterificada ou lipídios estruturados durante a fase de promoção inicial. O tratamento com lipídios estruturados demonstrou atividade quimiopreventiva comparável à da tributirina, mesmo resultando em menor concentração hepática de ácido butírico. Tanto a tributirina quanto os lipídios estruturados não inibiram a proliferação celular em lesões preneoplásicas, mas induziram a apoptose naquelas em remodelação. Os efeitos inibitórios da tributirina em fases iniciais da hepatocarcinogênese experimental estão relacionados ao aumento da acetilação de histonas e à modulação de processos de translocação nuclear da p53. No presente estudo, foi observado aumento substancial da razão nuclear/citoplasmática de p53 e importina-alfa em fígados de animais submetidos ao modelo e tratados com tributirina, mas não nos tratados com lipídios estruturados. Por outro lado, o tratamento com lipídios estruturados reduziu a expressão dos oncogenes Bcl2, Ccnd2, Pdgfa, Vegfa e aumentou a expressão dos genes supressores de tumor Cdh13, Fhit e Socs3. Assim, embora o potencial quimiopreventivo dos lipídios estruturados seja comparável ao da tributirina, os resultados sugerem que o novo composto não exibe atividade de HDACi, e que seus efeitos inibitórios na hepatocarcinogênese possam ser atribuídos à modulação da expressão de oncogenes e genes supressores de tumor

Combination of chemopreventive agents with different mechanisms of action has been considered a promising strategy to cancer prevention. Among several bioactive food compounds, tributyrin, a butyric acid prodrug obtained from dairy products and dietetic fiber fermentation, and flax seed oil, a rich source of alpha linolenic acid have shown chemopreventive potential. Here, we evaluated the chemopreventive activity of structured lipids obtained by enzymatic interesterification of tributyrin and flax seed oil during the early promotion phase of experimental hepatocarcinogenesis. Male Wistar rats subjected to the resistant hepatocyte model were treated daily, i.g, with maltodextrin, flax seed oil, tributyrin, non-sterified blend, or structured lipids. Treatment structured lipids showed similar chemopreventive activity compared to tributyrin, even when structured lipids yielded lower concentrations of butyric in the liver. Tributyrin and structured lipids did not inhibit cell proliferation in preneoplastic lesions, but both of them induced apoptosis in remodeling preneoplastic lesions. In addition, histone acetylation and p21 restored expression tributyrin molecular mechanisms were related to modulation of p53 nuclear shuttling mechanisms. In the present study, it was observed a substantial increase in p53 nuclear/cytoplasmic ratio and importin-alpha in preneoplastic livers of tributyrin treated rats, but not in those treated with structured lipids. In contrast, treatment structured lipids downregulated expression of major oncogenes Bcl2, Ccnd2, Pdgfa, and Vegfa; and upregulated expression of critical tumor suppressor genes, Cdh13, Socs3 and Fhit. Hence, although structured lipids and tributyrin show similar chemopreventive potential, the results suggest that the new compound does not exhibit HDACi activity, and that its inhibitory effects may be attributed to the modulation of oncogenes and tumor suppressor genes expression

Tratamiento de la hepatitis C en cirrosis: beneficios y riesgos / Treatment of hepatitis C in cirrhosis: risks and benefits

Hepatitis C virus infection is one of the main causes of liver disease affecting more than 180 million of people worldwide. In Chile it affects approximately 50,000 individuals. Chronic infection usually occurs with a long time of symptomless inflammation which defines a high risk of cirrhosis, hepatocellular carcinoma and liver transplantation. Effective antiviral therapy, defined as sustained virologic response (SVR) improves the prognosis of the infected subject. Current treatment regimens with direct acting antivirals have achieved high rates of therapeutic efficacy (SVR > 90 percent in different groups) with an appropriate safety profile. The addition of ribavirin increases the antiviral effect and reduces the duration of therapy. Cirrhotic patients are at greatest risk for developing complications, particularly liver cancer, and they have priority for treatment indication. Classically, cirrhotic show lower rates of effectiveness and high risk of adverse effects, but with the new antivirals, these patients can achieve high recovery rates. Therapy improves liver function and further decreases the viral reinfection after liver transplantation, so cirrhotic patients in the waiting list should be treated unless they have contraindications or high risk of side effects. Effective therapy is also associated with lower risk of developing hepatocellular carcinoma, but cirrhotic patients should keep vigilance programs despite effective treatment.

La infección crónica por virus de la hepatitis C es una de las principales causas de enfermedad hepática a nivel mundial, afectando a más de 180 millones de personas. En Chile, se estima que existen unos 50.000 infectados. La infección habitualmente cursa con largos períodos de inflamación asintomática que determinan un alto riesgo de desarrollo de cirrosis, carcinoma hepatocelular y trasplante hepático. La terapia antiviral efectiva, definida como respuesta viral sostenida (RVS) mejora el pronóstico global de los infectados. Los esquemas terapéuticos actuales, con antivirales de acción directa, han logrado altas tasas de eficacia terapéutica (RVS > 90 por ciento en la mayoría de los grupos) con un adecuado perfil de seguridad. El uso de ribavirina ha logrado potenciar el efecto antiviral y reducir la duración de la terapia. Los pacientes cirróticos son un grupo de mayor riesgo para el desarrollo de complicaciones, particularmente hepatocarcinoma, por lo que tienen prioridad para la indicación de tratamiento. Clásicamente, los cirróticos han tenido menores tasas de efectividad y alto riesgo de efectos adversos, pero con los nuevos antivirales, estos pacientes pueden lograr altas tasas de curación. La terapia mejora la función hepática y adicionalmente disminuye la reinfección viral post trasplante hepático, por lo que todos los cirróticos deberían tratarse pre trasplante, a menos que tengan contraindicaciones o alto riesgo de efectos adversos. La terapia efectiva también se asocia a menor riesgo de desarrollo de hepatocarcinoma, pero los pacientes cirróticos deben mantenerse en programas de seguimiento a pesar de un tratamiento efectivo.

Diagnóstico y tratamiento del hepatocarcinoma: puesta a punto del tema y rol del internista / Diagnosis and therapy of hepatocarcinoma: update of the topic and the internist’s role

El carcinoma hepatocelular es el tumor hepático maligno más frecuente, el 5o más prevalente en el mundo y la tercera causa de mortalidad por cáncer. En más de un 90% de los casos está asociado a cirrosis, su incidencia en dicha población es del 3 al 5%, siendo la primera causa de muerte en este grupo de pacientes. Se espera un incremento de esta incidencia en las próximas 2 décadas. En los últimos años se han desarrollado nuevas estrategias diagnósticas y terapéuticas que han modificado radicalmente el pronóstico de esta enfermedad. Al asentar sobre una patología donde el manejo médico es primordial el internista cumple un rol fundamental en el adecuado abordaje de esta neoplasia. Tareas como la prevención, la vigilancia, el diagnostico precoz y el enfoque multi e interdisciplinario, en los distintos estadios evolutivos de la enfermedad, son algunos de los aspectos más relevantes. El accionar con el médico hepatólogo es fundamental, definiendo en conjunto las distintas conductas a seguir en las instancias pre y postratamiento...

Imnunosupresión tras el trasplante hepático: más nefrones, menos hepatocarcinoma / Immunosupression after liver transplant: more nephrons, less hepatocellular carcinoma

Following liver transplantation, immunosuppressive drugs are responsible for a significant proportion of the morbidity and mortality. Thus, renal failure and hepatocellular carcinoma recurrence are critically related to the use of immunosuppressive drugs. In this article, the immunosuppressive strategies that allow preservation of the renal function and minimization of the recurrence rate of hepatocellular carcinoma are detailed.

Tras el trasplante hepático, la inmunosupresión es responsable de buena parte de la morbi-mortalidad asociada. El deterioro de la función renal y la recurrencia del hepatocarcinoma son ámbitos donde la inmunosupresión tiene un impacto significativo. En el presente artículo se abordan las estrategias inmunosupresoras que permiten preservar la función renal y minimizar la recurrencia del hepatocarcinoma tras el trasplante hepático.

Effect of sustained virologic response on the incidence of hepatocellular carcinoma in patients with HCV cirrhosis

BACKGROUND AND OBJECTIVES: Evidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma. METHODS: A cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy. RESULTS: The mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55 percent) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3 percent) vs. 8 (17 percent) responders and non responders respectively (p = 0.02). CONCLUSION: Patients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.

Prevenção do carcinoma hepatocelular / Prevention of hepatocellular carcinoma

INTRODUÇÃO: O carcinoma hepatocelular (CHC) é uma das principais doenças malignas da atualidade. Devido à alta incidência e prognóstico habitualmente sombrio torna-se relevante a necessidade de ações preventivas, levando em consideração a característica peculiar de sua etiologia: estrita relação de sua gênese a fatores ambientais. Os principais fatores de risco geograficamente melhor distribuídos são a associação de CHC com infecções por hepatite B crônica, hepatite C e cirrose hepática (associação em mais de 80% dos casos), independente de seu fator causal. Ele é o quinto tumor maligno mais frequente em todo o mundo (5º em homens e 8º em mulheres); representa 85% dos tumores hepáticos primários e é responsável por quase dois terços das mortes por câncer. MÉTODO: Revisão da literatura nacional e internacional dos últimos 12 anos (1997-2009), de 25 artigos pesquisados nas bases eletrônicas de dados MedLine, Scielo e LILACS. CONCLUSÃO: Apesar dos avanços científicos e da implementação de medidas para detecção precoce do CHC em pacientes pertencentes a grupos de risco, não houve melhora na taxa de sobrevida durante as três últimas décadas. O motivo que pode explicar esse fato é que a maioria dos pacientes começa a apresentar sintomas...

BACKGROUND: Hepatocellular carcinoma is one of the major malignant diseases in the world today. Due to the high incidence and difficult prognosis, preventive measures became an important need taking into consideration that its etiology is strictly connected with environmental factors. The main risk factors are the association of hepatocellular carcinoma with chronic hepatitis B and C virus infections and cirrhosis, whatever its cause. Hepatocellular carcinoma is the fifth most common global cancer, representing 85% of the hepatic primary tumors and it is responsible for nearly two thirds of deaths caused by cancer. METHOD: Review of the national and international literature in the last 12 years (1997-2009), of 25 articles researched through the electronic databases MedLine, Scielo and Lilacs. CONCLUSION: Despite of the medical advances and the implementation of precocious measures to detect the hepatocellular carcinoma in patients considered as within risk groups, there was no improvement on the afterlife over the last three decades. The cause that can explain this reality is the absence of symptoms during the early stages of the disease, and by the time the patient looks for medical help, the tumor has frequently reached an advanced stage and the therapeutical options are already too few.

Prevention of Hepatocelluar Carcinoma / 대한소화기학회지

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has the third highest mortality rate among malignancies in South Korea. Despite the continuing efforts for the early detection of HCC, the mortality rate and prognosis have not been improved yet. Its clinical behavior is quite different from other cancers. High recurrence rate after curative treatment might be the reason for poor prognosis. Several methods including chemoprevention, blocking the development of HCC, have been under investigations. The vaccine for hepatitis, in the form of primary prevention, is considered to be the most effective one inhibiting the development of liver disease. Furthermore, keeping away from hepatotoxic agents is another way for preventing liver cell injuries. Secondary prevention is to stop the developement of HCC in chronic liver diseases. Since the level of DNA in hepatitis B virus (HBV) hepatitis patients is closely related with the development of HCC, it is helpful to lower the DNA level using anti-viral agents. In addition, IFN, one of the anti-viral agents, can inhibit HCV hepatitis from tumorigenesis. Cyclo-oxygenase (COX)-2 inhibitors are also alleged to have a function in interrupting the development of HCC. Tertiary prevention means the prevention of recurrence of HCC after successful treatment. Because of high recurrence rate, the prevention of recurrence should be one of the important factors affecting the prognosis of HCC. Up to now, COX inhibitors, retinoic acids, vitamin K2, glycyrrhizin epigallocatechin-3-gallate (EGCG), and ginseng had been reported to be effective for the chemoprevention of HCC. Further studies are required for an advancement in the prevention of HCC.

[Passive and active immunization in prevention of vertical transmission of HBV infection in infants of HBsAg positive mothers]

In order to prevent liver cirrhosis and hepatocellular carcinoma in later life, it is essential to prevent Hepatitis B virus [HBV] infection in infants. Despite the availability of an effective vaccine, hepatitis B still continues to be a significant health problem. The aim of this study is to reveal the efficacy of passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus in Iran. In this cohort study with historical controls, 823 children of the HBsAg positive mothers were evaluated. There were 637 cases who had received neither Hepatitis B [HB] vaccine nor hepatitis B immunoglobulin [HBIG], 125 persons received only HB vaccine and 60 neonates that we administered them HB vaccine and HBIG together. The prevalence of HBsAg in cases who have received neither vaccine nor HBIG and aged > 16 years [group1] or <= 16 years [group 2], cases who have received vaccine alone [group 3], and in cases who have received both vaccine and HBIG [group 4] was 56.1%, 40.3%, 12.6%, and 3.6%, respectively. The prevalence of HBsAb had a significant descending rate in groups 4 [85.7%], 3 [68.8%], 2 [33.3%], and 1 [21.8%] respectively. The addition of HBIG to recombinant vaccine will significantly increase the protection against HBV infection in comparison with HB vaccine without HBIG. After focusing on the vertical route for many years, and implementing strategies such as vaccination and HBIG injection to neonates of HBsAg positive mothers, nowadays it seems that we should pay more attention to horizontal way of HBV transmission in Iran

Hepatocellular carcinoma

To establish the most common pathological criteria to diagnose hepatocellular carcinoma, and to identify the high-risk patients for further investigation in order to detect hepatocellular carcinoma in its early stages. A retrospective study was carried out at King Khalid National Guard Hospital including 60 cases diagnosed as hepatocellular carcinoma cytologically and histopathologically. Further investigations were performed by special staining and immunohistochemical staining on 42 blocks including Periodic acid-schiff, PAS-D, Reticulin, Iron and Alpha Fetoprotein, hepatitis B surface antigen, hepatitis B core antigen and p53 antibodies. It was found that pleomorphism, followed by presence of prominent nucleoli and nuclear pseudoinclusion were the most frequent finding in hepatocellular carcinoma. While considering other studies, reticulin framework, glycogen and iron content of the hepatocellular carcinoma were markedly diminished as compared to non-malignant liver tissue. Antibodies against tumor suppressor gene was applied on paraffin section [p53], it was positive in 52% of cases and 53% of them were having anti hepatitis B surface antigen positivity, detected in their serum and 23% were having hepatitis C antibodies positive. Hepatocellular carcinoma is a common malignancy that can be detected by certain defined pathological parameters and should be suspected in high-risk patient

Long-term follow up of Egyptian patients with chronic hepatitis c: impact of interferon therapy on their outcome - with special reference to HCC

To our knowledge no previous data worldwide investigated the effects of interferon therapy in the treatment of hepatitis C virus [HCV] for longer than two years. So, this study was conducted to address the longer-term [3.5 years] Group II: 59 patients, chronic HCV with no cirrhosis, [interferon group-I] received interferon 3MIU every other day for 6 months. 57 patients completed the interferon therapy as 2 patients excluded during interferon therapy.outcomes of clinical, virological, biochemical and clinical responses to interferon therapy and the change in incidence of hepatocellular carcinoma [HCC] and other HCV-related complications in-patients with chronic hepatitis C with and without liver cirrhosis. 139 patients in our study were classified into 4 groups: Group I: 20 patients, chronic HCV with no cirrhosis, [control group-1] received silymarin 70 mg thrice daily for 3.5 years. Group III: 20 patients, chronic HCV with cirrhosis, [control group-2] received silymarin 70mg thrice daily for 3.5 years. Group IV: 40 patients, chronic HCV with cirrhosis, [interferon group-2] received interferon 3MIU every other day. for 6 months. Evaluation of our patients during the study period was based on the followings: 1] Response at the end of interferon therapy and 3 years after interferon withdrawal. 2] Incidence of liver decompensation. 3] Incidence of portal hypertension 4] Incidence of gastrointestinal bleeding. 5] Incidence of hepatocellular carcinoma. 1- Interferon alpha is effective in chronic hepatitis C and 49% of patients obtain a sustained benefit [long-term responders]. 2-The sustained response to interferon therapy in patients with chronic hepatitis C with cirrhosis is 0% after 3 years of stop interferon. 3-Interferon therapy significantly reduces the risk of developing portal hypertension, ascites and hepato-cellular carcinoma in patients with HCV cirrhosis irrespective of the virological response to interferon. - Early treatment of patients with chronic hepatitis C before reaching the stage of cirrhosis.- Proper selection of patient who is candidate for interferon therapy to increase the response rate. Cirrhosis should not be considered a reason for excluding patients with HCV- related liver disease from interferon therapy

Ultraestructura del hepatocito en diversas hepatopatías / Hepatocyte ultrastructure in liver diseases

Se estudiaron 14 biopsias hepáticas obtenidas de ocho pacientes con hepatitis viral aguda y series con hepatopatías crónicas, y se halló buena correlación de los datos clínicos con las alteraciones morfológicas por lo que parece recomendable hacer una clasificación etiológica para evitar que los pacientes progresen a cirrosis y desarrollen carcinoma hepatocelular. El estudio de la hepatitis viral mediante los microscopios de luz y electrónico de transmisión, correlacionado con la clínica y completado con estudios de histoquímica y virología, sirven para aclarar interrogantes en relación a la identificación del virus

Carcinoma hepatocelular / Hepatocellular carcinoma

O carcinoma hepatocelular (CHC) é um dos tumores malignos mais freqüentes no mundo, sendo considerado pela OMS como problema de Saúde Pública em áreas de grande incidência do tumor, como Africa e Sudeste Asiático. Nesta revisäo seräo discutidos alguns aspectos do CHC, especialmente: a) a estreita relaçäo etiológica com o vírus da hepatite B, o mais universal agente etiológico, mas näo o único, havendo outros carcinogénicos e co-carcinogénicos que participam da gênese do tumor; b) a grande variaçäo na distribuiçäo geográfica do tumor, inclusive no Brasil, onde ele é mais freqüente no Norte e Nordeste; c) a singular associaçäo com a cirrose hepática, observada em todas as regiöes onde o tumor é diagnosticado; d) aspectos morfológicos do CHC, incluindo a nova classificaçäo macroscópica baseada nos padröes de crescimento do tumor e as características dos CHC pequenos; e) as manifestaçöes clínicas e alteraçöes laboratoriais, dando ênfase à avaliaçäo da alfa-feto-proteína, nem sempre elevada nos pacientes com CHC e aos métodos de imagenologia, especialmente a ultra-sonografia, como métodos para o diagnóstico precoce do CHC, o que melhora o prognóstico, sendo importante o seguimento de pacientes de alto risco (cirróticos HBsAg positivos) com aqueles métodos. Finalmente seräo feitos comentários sobre terapêutica, quando esta é possível, e sobre a perspectiva de prevençäo da ocorrência do tumor pelo aumento na utilizaçäo da vacina contra o VHB