Hepatocellular Carcinoma (HCC)

Ferenci, Péter; Fried, Michael; LaBrecque, Douglas R.; Bruix, Jordi; Sherman, Morris; Omata, Masao; Heathcote, Jenny; Piratsivuth, Teehra; Kew, Mike; Otegbayo, Jesse Abiodun; Zheng, Shi; Sarin, Simran; Hamid, Saeed; Modawi, Salma Barakat; Fleig, Wolfgang E.; Fedail, S S; Thomson, Allan D.; Khan, Aamir Ali; Malfertheiner, Peter; Lau, George; Carillo, Flair J.; Krabshuis, Justus; Mair, Anton Le

doi:10.1097/mcg.0b013e3181d46ef2

Cited by 271 publications

(175 citation statements)

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“…2 Approximately 50% of HCC cases worldwide can be attributed to chronic HBV infection (CHB) and almost 75% of HCC cases occur in developing countries where HBV is endemic. 3,4 According to statistics, older male patients who are infected with HBV genotype C or co-infected with HCV, have high levels of viral load and have been exposed to the aflatoxin, or older male patients who have a family history of HCC tend to have a high risk of developing HCC. [5][6][7] Accumulating clinical and epidemiological evidence shows a significant correlation between chronic HBV infection and hepatocarcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono-and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC. Keywords: activating receptor; hepatocellular carcinoma; inhibitory receptor; natural killer cell; natural killer receptor INTRODUCTION Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. 1 Common clinical risk factors for HCC include hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, heavy alcohol intake, steatohepatitis and diabetes. 2 Approximately 50% of HCC cases worldwide can be attributed to chronic HBV infection (CHB) and almost 75% of HCC cases occur in developing countries where HBV is endemic. 3,4 According to statistics, older male patients who are infected with HBV genotype C or co-infected with HCV, have high levels of viral load and have been exposed to the aflatoxin, or older male patients who have a family history of HCC tend to have a high risk of developing HCC. [5][6][7] Accumulating clinical and epidemiological evidence shows a significant correlation between chronic HBV infection and hepatocarcinogenesis. However, the underlying mechanisms

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Section: Introductionmentioning

confidence: 99%

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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“…[5][6][7][8] Various etiologies, including hepatotropic viruses (eg, hepatitis B and C viruses), chronic alcohol consumption, nonalcoholic steatohepatitis, and toxins (eg, aflatoxin B), can lead to chronic liver injury, inflammation, or fibrosis/cirrhosis, which can then culminate in liver cancer. [1][2][3] Although the close contributory relationship between chronic liver inflammation and carcinogenesis has been well documented, 2,3 the exact mechanisms that direct inflammation-induced liver cancer remain elusive.…”

mentioning

confidence: 99%

“…1,2 Despite recent progress in understanding its pathogenic mechanisms, [2][3][4] HCC is still considered one of the deadliest cancers worldwide with a poor prognosis, as very few patients are eligible for potential curative treatment, such as surgical resection and liver transplantation. [5][6][7][8] Various etiologies, including hepatotropic viruses (eg, hepatitis B and C viruses), chronic alcohol consumption, nonalcoholic steatohepatitis, and toxins (eg, aflatoxin B), can lead to chronic liver injury, inflammation, or fibrosis/cirrhosis, which can then culminate in liver cancer.…”

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confidence: 99%

Hepatoprotective versus Oncogenic Functions of STAT3 in Liver Tumorigenesis

Wang

Lafdil

Wang

et al. 2011

The American Journal of Pathology

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Aberrantly hyperactivated STAT3 has been found in human liver cancers as an oncogene; however, STAT3 has also been shown to exert hepatoprotective effects during liver injury. The balancing act that STAT3 plays between hepatoprotection and liver tumorigenesis remains poorly defined. In this study, the diethylnitrosamine (DEN)-induced liver tumor model and the chronic carbon tetrachloride (CCl 4 )-induced liver fibrosis model were both used to investigate the role of STAT3 in liver tumorigenesis. Hepatocyte-specific STAT3 knockout mice were resistant to liver tumorigenesis induced by a single DEN injection, whose tumorigenesis was associated with minimal chronic liver inflammation, injury, and fibrosis. In contrast, long-term CCl 4 treatment resulted in severe hepatic oxidative damage, inflammation, and fibrosis but rarely induced liver tumor formation in wild-type mice. Despite the oncogenic function of STAT3 in DEN-induced liver tumor, hepatocyte-specific STAT3 knockout mice were more susceptible to liver tumorigenesis after 16 weeks of CCl 4 injection, which was associated with higher levels of liver injury, inflammation, fibrosis, and oxidative DNA damage compared with wild-type mice. These findings suggest that the hepatoprotective feature of STAT3 prevents hepatic damage and fibrosis under the condition of persistent inflammatory stress, consequently suppressing injurydriven liver tumor initiation. Once liver tumor cells have developed, STAT3 likely acts as an oncogenic factor to promote tumor growth.

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“…Among all staging systems proposed until now, the most relevant and successful one has been Barcelona Clinic Liver Cancer (BCLC) staging system. Since its former publication in 1999 (37), BCLC classification has been continuously refined to its last version in 2014 (38), it has been externally validated (39)(40)(41)(42) and because of its very well known predictive ability and its utility for clinical decision making, this staging system is the recommended one by the most relevant scientific societies (5,6,43,44). A new staging system called Hong Kong Liver Cancer (HKLC) staging system has been recently published.…”

Section: Refining Prognostic Assessment and Therapeutic Decisionmentioning

confidence: 99%

New challenges in clinical research on hepatocellular carcinoma

Díaz-González¹,

Forner²,

C³

et al. 2015

Rev Esp Enferm Dig

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This is an updated review of screening, early diagnosis and treatment of hepatocellular carcinoma, focusing on the advancements occurred in the last years and highlighting the challenges in clinical research.Hepatocellular carcinoma (HCC) is nowadays the sixth most frequent cancer worldwide with up to 740,000 new cases diagnosed each year, and it is the third most prevalent cause of cancer-relateddeath worldwide (1). This neoplasm usually appears linked to an underlying liver disease, being one of the most relevant causes of death in patients diagnosed of liver cirrhosis (2,3). In the last years, important advancements in terms of diagnosis, staging and treatment of HCC, improving the management and outcome of the disease, have been made (4-7). Despite the fact that these improvements have absolutely changed natural history of HCC, there are several areas that still need further advancements.The aim of this document is to discuss some controversial aspects, which in our opinion constitute real challenges in clinical research of HCC.Key words: Hepatocellular carcinoma. Hepatic oncology. Sorafenib. Transarterial chemoembolization. AFP. IMPROVING EARLY DIAGNOSISFrom the basis that the only possibility to offer and apply treatments with curative intention is being able to diagnose HCC at early stages, when there are not cancer related symptoms. Since this option is only feasible if screening is performed in population at risk, scientific guidelines recommend performing abdominal ultrasonography (US) in every patient with liver cirrhosis. Despite the recommendation of HCC screening by the Spanish guidelines (4), one registry study performed in Spain which included 62 centers and 705 patients diagnosed of HCC within a period of time of 4 months showed that just 47% of HCC patients were diagnosed in the setting of surveillance and less than a half were diagnosed at early stage (8).This data shows that early diagnosis, a key issue to be able to significantly reduce HCC-related mortality, is one of the most relevant issues that deserve further efforts from scientific community. Aiming to evaluate which were the causes of screening program fail in the United States of America, Singal et al. evaluated 1,005 patients included in the HALT-C prospective study. A third part of patients did not adhere to an adequate screening program and, in 70% of cases that were diagnosed at an advanced stage, the main reason was the absence of detection in US (9).With the aim of improving detection rate, it is crucial to establish formative programs in order to certify the capability of being able to carry on this activity and it is necessary to use up-to-date ultrasonography scans in order to perform an optimal liver exploration. Tumor markers could be a useful tool to overcome theoretical limitations of US: its evaluation is not subjective, does not depend on the operator and it may be reproducible, as well as it is relatively cheap and a tool easy to access in areas with low monetary income. Regrettably, different tumor markers ev...

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Hepatocellular Carcinoma (HCC)

Cited by 271 publications

References 1 publication

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

Hepatoprotective versus Oncogenic Functions of STAT3 in Liver Tumorigenesis

New challenges in clinical research on hepatocellular carcinoma

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