HCV-associated hepatocellular carcinoma -without cirrhosis (original) (raw)
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Hepatitis C virus infection in the development of hepatocellular carcinoma in cirrhosis
Journal of Hepatology, 1997
Backgvoun&Xms: The role of hepatitis C virus replication and different genotypes in the progression of cirrhosis to hepatocellular carcinoma is examined on the basis of a prospective follow-up of 1438 patients with histologically proven cirrhosis. Methods: The presence of HCV RNA, anti-HCV and characterisation of virus genotypes were determined in 72 cases who developed hepatocellular carcinoma after a median follow-up of 5.3 years (range 1 to 16) and compared to 72 controls who had cirrhosis only, after a median follow-up of 4.8 years (range 1 to 16). Patients in the hepatocellular carcinoma group and controls were matched, one to one, for age, sex, nationality, HBsAg seropositivity, duration of followup and aetiology of cirrhosis. Results: HCV RNA was detected in 31 of 72 (44%) patients who developed hepatocellular carcinoma, significantly more frequently than in 17 of 72 (23%) controls with cirrhosis (odds ratio 2.4, 95% confidence LTHOUGH the pathogenesis of hepatocellular carci-
Hepatitis C virus-induced hepatocellular carcinoma
Clinical and Molecular Hepatology, 2015
Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs. (Clin Mol Hepatol 2015;21:105-114)
Hepatitis C and hepatocellular carcinoma: A review of natural history
Journal of Medicine, Radiology, Pathology and Surgery, 2016
The main causative factor for the chronic liver disease is infection with hepatitis C virus (HCV). Around the world, it has been estimated that almost 180 million people are carriers of HCV. Infection with HCV leads to hepatocellular carcinoma (HCC) that is a frequent cause of mortality in HCV-infected patient. Among the most common cancers, it is ranked fifth worldwide. The annually death rate of HCC patients being caused by HCV is approximately 1 million. Epidemiological studies have demonstrated that prolong infection with HCV is the main threat for the development of HCC. Keeping the knowledge about the causes of cirrhosis and development of HCC in HCV patients is consequently very important for improving treatment choices and health-care delivery. Effective precautionary measures that can prevent the progression of HCC have now been well illustrated. The perfect natural explanation of HCC pathogenesis is so diverse that treatment strategies are highly difficult. Therefore, in the case of nonmalignant hepatic disease follow-up of the patients and treatment options must take into account to prevent the progression to carcinoma. In this review, we have strived to describe natural disease course of HCV infection and the ways through which it progresses to malignant hepatic disease.
2011
More than one and half of current cases of hepatocellular carcinoma in the US, Europe, and Japan are attributable to hepatitis C virus (HCV) infection. HCV is also the primary cause of death in patients with HCV-related cirrhosis, with annual incidences of 0.5%-5% in Europe and 4%-10% in Asia. Screening is based on serum alpha-fetoprotein determination and liver ultrasound scan, but the sensitivity of the former is far less than optimal, and screening intervals are still poorly defined for the latter. Risk factors related to the host or environment, or both, appear to be more relevant than viral factors, such as HCV genotype, in determining disease progression to cirrhosis and cancer, and include age, male gender, severity of liver disease at presentation, coinfection with hepatitis B virus or human immunodeficiency virus, and alcohol abuse. Early liver transplantation in selected cases can be curative, but most patients are not eligible for liver grafting and are treated with locoregional ablative therapies, after which recurrence is common. Recently, orally available inhibitors of the vascular endothelial growth factor receptor have shown a significant, albeit modest, increment of survival in patients with advanced hepatocellular carcinoma, thus paving the way for modern molecular approaches to treatment of this highly malignant tumor.
Hepatitis C virus and hepatocellular carcinoma
Best Practice & Research Clinical Gastroenterology, 1999
The sequential development of cirrhosis and hepatocellular carcinoma (HCC) in patients with transfusion-associated hepatitis was a clue leading to the identi®cation of hepatitis C virus (HCV) as a risk factor for HCC. The incidence of HCV-related liver cancer is increasing in many developed countries: tumours arise in older patients, are almost invariably associated with cirrhosis and often have a less aggressive course than is seen in HCC related to other aetiological factors. Most HCCs grow as a single hepatic nodule for several years before generating satellite or distant tumour nodules. Tumour progression and hepatic failure are the leading causes of death. HCV might promote cancer through cirrhosis, which is per se an important risk factor for this tumour. HCV might also have oncogenic properties by interacting with cellular genes that regulate cell growth and dierentiation. The primary prevention of HCC through vaccination against HCV is not yet available. The treatment of patients with chronic hepatitis C with interferon might attenuate the risk of HCC.
Molecular Aspects of Hepatocellular Carcinoma Caused by Hepatitis C Virus
The hepatitis C virus (HCV) is a small, enveloped, single-stranded positive-sense RNA virus with a diameter of about 50 nm belonging to the Hepacivirus genus of the family Flaviviridae. The HCV genome is translated to produce a single protein of around 3011 amino acids. This "polyprotein" is then proteolytically processed by viral and cellular proteases to produce structural (core protein, envelope glycoproteins E1 and E2, ARFP/F protein, p7) and nonstructural (NS2-3 autoprotease, NS3-4A, NS4B, NS5A, NS5B) proteins. Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide, with increasing incidence. It is estimated that approximately 300-400 thousands of people in the IRAN and 4 million in the United States are persistently infected. It is important for tumor control to identify the factors that predispose patients to death. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. Keywords: Hepatitis C virus (HCV), Hepatocellular carcinoma, Genomic and Proteomics
Hepatitis C virus-induced hepatocarcinogenesis
Journal of Hepatology, 2009
Although there is strong evidence that hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma (HCC), there is still much to understand regarding the mechanism of HCV-induced transformation. While liver fibrosis resulting from long-lasting chronic inflammation and liver regeneration resulting from immune-mediated cell death are likely factors that contribute to the development of HCC, the direct role of HCV proteins remains to be determined. In vitro studies have shown that HCV expression may interfere with cellular functions that are important for cell differentiation and cell growth. However, most studies were performed in artificial models which can only give clues for potential mechanisms that need to be confirmed in more relevant models. Furthermore, the difficulty to identify HCV proteins and infected liver cells in patients, contributes to the complexity of our current understanding. For these reasons, there is currently very little experimental evidence for a direct oncogenic role of HCV. Further studies are warranted to clarify these issues.
Liver International, 2009
Background/Aims: The mechanism of hepatocarcinogenesis remains unclear in patients in whom hepatitis C virus (HCV) disappears after interferon (IFN) therapy. We compared molecular alterations in hepatocellular carcinoma (HCC) between patients with a sustained virological response (SVR) to IFN and patients with HCV. Methods: The study group comprised 44 patients with HCV and 13 patients with SVR. One patient in the SVR group had two tumour nodules, both of which were examined. Mitochondrial DNA (mtDNA) mutations in displacement-loop lesions were directly sequenced. Mutation of the TP53 gene was examined by direct sequencing. The methylation status of p16, p15, p14, RB and PTEN genes was evaluated by a methylation-specific polymerase chain reaction. Results: The average number of mtDNA mutations was 4.2 in 44 HCCs with HCV and 2.0 in 14 HCCs with SVR (P = 0.0021). mtDNA mutation was less frequently detected in HCCs from patients with SVR than in patients with HCV. TP53 mutations were detected in 12 (27%) of 44 HCCs with HCV and 2 (14%) of 14 SVR-HCCs. Hypermethylation of the p16, p15, p14, RB and PTEN promoters was, respectively, detected in 34, 13, 8, 12 and 11 of 44 HCCs from patients with HCV and 14, 0, 0, 2 and 2 of 14 HCCs from patients with SVR (P = 0.049, 0.021, 0.085, 0.322 and 0.402). Hypermethylation of p16 was one of the most important alterations in SVR-HCC. Conclusions: Molecular alterations in hepatocarcinogenesis of patients with SVR-HCC were different from those of patients with continuous HCV infection.