Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver disease

Trinchet, Jean–Claude; Ganne-Carrié, Nathalie; Nahon, Pierre; N’Kontchou, Gisèle; Beaugrand, Michel

doi:10.3748/wjg.v13.i17.2455

Cited by 29 publications

(16 citation statements)

References 65 publications

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“…The virus genome is a positive-stranded RNA of about 9,600 nucleotides, which contains a single open reading frame (ORF) encoding both structural (core, E1, E2, and p7) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) proteins (47). Two highly conserved untranslated regions (UTRs) are found at the 5Ј and 3Ј ends, which play critical roles in both viral translation and replication (13,14,23).HCV is estimated to infect 170 million people worldwide (1, 43) and in a high percentage of individuals causes a chronic liver infection that frequently evolves into an array of diseases, including cirrhosis (12, 15, 38) and hepatocellular carcinoma (4,7,17,30,38,49).The HCV RNA-dependent RNA polymerase (NS5B) has a high frequency of incorrect nucleotide insertions, in the range of 10 Ϫ4 to 10 Ϫ5 base substitutions per site, which can result in the rapid generation of HCV quasispecies (37, 45). Because of this huge genetic diversity, HCV is currently classified into six major genotypes and more than 80 subtypes (44).…”

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confidence: 99%

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Naturally Occurring Hepatitis C Virus Subgenomic Deletion Mutants Replicate Efficiently in Huh-7 Cells and Are trans -Packaged In Vitro To Generate Infectious Defective Particles

Pacini¹,

Graziani²,

Bartholomew³

et al. 2009

J Virol

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Naturally occurring hepatitis C virus (HCV) subgenomic RNAs have been found in several HCV patients. These subgenomic deletion mutants, mostly lacking the genes encoding envelope glycoproteins, were found in both liver and serum, where their relatively high abundance suggests that they are capable of autonomous replication and can be packaged and secreted in viral particles, presumably harboring the envelope proteins from wild type virus coinfecting the same cell. We recapitulated some of these natural subgenomic deletions in the context of the isolate JFH-1 and confirmed these hypotheses in vitro. In Huh-7.5 cells, these deletioncontaining genomes show robust replication and can be efficiently trans-packaged and infect naïve Huh-7.5 cells when cotransfected with the full-length wild-type J6/JFH genome. The genome structure of these natural subgenomic deletion mutants was dissected, and the maintenance of both core and NS2 regions was proven to be significant for efficient replication and trans-packaging. To further explore the requirements needed to achieve trans-complementation, we provided different combinations of structural proteins in trans. Optimal trans-complementation was obtained when fragments of the polyprotein encompassing core to p7 or E1 to NS2 were expressed. Finally, we generated a stable helper cell line, constitutively expressing the structural proteins from core to p7, which efficiently supports trans-complementation of a subgenomic deletion encompassing amino acids 284 to 732. This cell line can produce and be infected by defective particles, thus representing a powerful tool to investigate the life cycle and relevance of natural HCV subgenomic deletion mutants in vivo.Hepatitis C virus (HCV) is an enveloped virus belonging to the family Flaviviridae. The virus genome is a positive-stranded RNA of about 9,600 nucleotides, which contains a single open reading frame (ORF) encoding both structural (core, E1, E2, and p7) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) proteins (47). Two highly conserved untranslated regions (UTRs) are found at the 5Ј and 3Ј ends, which play critical roles in both viral translation and replication (13,14,23).HCV is estimated to infect 170 million people worldwide (1, 43) and in a high percentage of individuals causes a chronic liver infection that frequently evolves into an array of diseases, including cirrhosis (12, 15, 38) and hepatocellular carcinoma (4,7,17,30,38,49).The HCV RNA-dependent RNA polymerase (NS5B) has a high frequency of incorrect nucleotide insertions, in the range of 10 Ϫ4 to 10 Ϫ5 base substitutions per site, which can result in the rapid generation of HCV quasispecies (37, 45). Because of this huge genetic diversity, HCV is currently classified into six major genotypes and more than 80 subtypes (44). Recombination may be another mechanism exploited by HCV to increase genetic diversity: naturally occurring intergenotypic recombinant viruses that often have their recombination points in the trans-membrane domains of NS2 were recently i...

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confidence: 99%

“…HCV is estimated to infect 170 million people worldwide (1, 43) and in a high percentage of individuals causes a chronic liver infection that frequently evolves into an array of diseases, including cirrhosis (12, 15, 38) and hepatocellular carcinoma (4,7,17,30,38,49).…”

mentioning

confidence: 99%

Naturally Occurring Hepatitis C Virus Subgenomic Deletion Mutants Replicate Efficiently in Huh-7 Cells and Are trans -Packaged In Vitro To Generate Infectious Defective Particles

Pacini¹,

Graziani²,

Bartholomew³

et al. 2009

J Virol

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“…In our series, all patients were cirrhotic. The most prevalent cause in Europe is HCV infection (25). Over one-half of our patients presented HCV infection, associated or not to alcohol abuse.…”

Section: Discussionmentioning

confidence: 80%

Factors related to survival in hepatocellular carcinoma in the geographic area of Sabadell (Catalonia, Spain)

Miquel

Sopeña

Vergara

et al. 2012

Rev. esp. enferm. dig.

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BAckground: hepatocellular carcinoma (HCC) is a very frequent tumor. Screening for the disease is effective, but the prognostic factors are difficult to evaluate.Objectives: 1. To determine epidemiological data and the clinical course of HCC in our setting. 2. To compare patient survival according to whether screening is performed or not. 3. To evaluate survival prognostic factors.Patients and methods: data on the epidemiology and clinical course of patients diagnosed with HCC were collected on a prospective basis (January 2004-December 2006. Two groups were considered according to whether screening had been performed (group A) or not (group B).Results: a total of 110 patients were diagnosed with HCC (70% males). The most common etiology of cirrhosis was hepatitis C (56.1%), and 69% presented mild liver failure (Child-Pugh grade A). The median follow-up was 1.8 years. Fifty-one percent had been subjected to screening. The diagnosis of HCC was established by imaging techniques in 48.2% of the cases, and by histological criteria in 51.8%. The median tumor size was 23 mm in group A and 28 mm in group B (p = 0.005). Treatment with curative intent was provided in 72% of the cases in group A and in 48% in group B (p = 0.011). The median overall survival was 1.99 years -2.67 years in group A and 1.75 years in group B (p = 0.05).The multivariate analysis of overall survival showed the type of treatment (OR = 2.82 95%CI: 1.3-6.12, p = 0.009) and liver function (OR = 1.71 95%CI: 1.1-2.68, p = 0.020) to be independent predictors of survival.Conclusions: screening allows the diagnosis of smaller lesions and a higher percentage of curative treatments. The degree of liver function and the provision of curative treatment are independent predictors of survival.

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“…Una única LOEH tuvo una supervivencia de 26,91 IC 95% (21,46). Dos LOEH tuvieron una supervivencia de 30,30 IC 95% (14,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)31). La presencia CHC multifocal tuvo una supervivencia de 10,20 IC 95% (3,89-16,51) (p < 0,05).…”

Section: Evolución De Los Pacientesunclassified

Historia natural del carcinoma hepatocelular en una cohorte de pacientes de un hospital comarcal

Vergara

Gil

Dalmau

et al. 2008

Rev. esp. enferm. dig.

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RESUMENIntroducción: el carcinoma hepatocelular (CHC) es una neoplasia con una elevada incidencia y una alta mortalidad.Objetivo: nuestro objetivo es la descripción de la historia natural de una cohorte de pacientes con CHC e identificar variables asociadas a supervivencia.Material y métodos: estudio retrospectivo y descriptivo de pacientes diagnosticados de CHC entre 1995de CHC entre -2002. Las variables cualitativas se expresaron mediante frecuencias y porcentajes y las cuantitativas con mediana y desviación típica. La supervivencia se estimó mediante el método de Kaplan Meyer y la prueba de Log Rank.Resultados: se analizaron un total de 154 pacientes con CHC. La ratio hombre-mujer fue de 2,9/1. La edad media de 68 ± 9 años. El 82% de los pacientes fueron exitus en un tiempo medio de seguimiento de 28 meses. La mediana de supervivencia fue de 21,5 meses (IC 95%: 16,04). Se realizó tratamiento con intención curativa en un 40,3% y el resto tratamiento paliativo. Las variables asociadas a la supervivencia fueron: presencia o no de ascitis, el nú-mero de lesiones en el momento del diagnóstico y si el tratamiento realizado fue con intención curativa o no. No hubieron diferencias estadísticamente significativas respecto a: sexo, edad, etiología de la cirrosis y estadio de Child en el momento del diagnóstico.Conclusiones: los factores asociados a una menor supervivencia en los pacientes con carcinoma hepatocelular fueron la presencia de ascitis y el número de lesiones en el momento del diagnóstico. La realización de tratamiento con intención curativa se asocia a una mayor supervivencia.Palabras clave: Carcinoma hepatocelular. Cirrosis hepática. Screening. Supervivencia. Ascitis. ABSTRACTBackground: hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality.Objective: our aim was to describe the natural history of a patient cohort with HCC, and to identify the factors associated with survival.Patients and methods: a retrospective and descriptive study of patients diagnosed with HCC between 1995 and 2002. Qualitative variables were expressed as frequencies and percentages. Quantitative variables were expressed as medians and standard deviations. Survival was calculated using the Kaplan-Meier method and log rank.Results: a total of 154 patients were analyzed. The men-towomen ratio was 2.9/1. Mean age was 68 ± 9 years. 82% of patients died during a median follow-up of 28 months. Median survival was 21.5 months (95% CI: 16.98-26.04). Curative treatment was done in 40.3% of diagnosed patients, and 59.7% of patients received palliative treatment. Factors associated with survival were: ascites, number of lesions at diagnosis, and curative treatment. No statistical differences were found for the next factors: age, sex, etiology of cirrhosis, and Child-Pugh stage at diagnosis.Conclusions: factors associated with low survival in patients with HCC were ascites and number of lesions. Curative treatment is associated with a higher survival when compared to palliative treatment.

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Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver disease

Cited by 29 publications

References 65 publications

Naturally Occurring Hepatitis C Virus Subgenomic Deletion Mutants Replicate Efficiently in Huh-7 Cells and Are trans -Packaged In Vitro To Generate Infectious Defective Particles

Naturally Occurring Hepatitis C Virus Subgenomic Deletion Mutants Replicate Efficiently in Huh-7 Cells and Are trans -Packaged In Vitro To Generate Infectious Defective Particles

Factors related to survival in hepatocellular carcinoma in the geographic area of Sabadell (Catalonia, Spain)

Historia natural del carcinoma hepatocelular en una cohorte de pacientes de un hospital comarcal

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