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Review
. 2018 Oct 21;24(39):4436-4447.
doi: 10.3748/wjg.v24.i39.4436.

Carcinogenesis on the background of liver fibrosis: Implications for the management of hepatocellular cancer

Joanne Marie O'Rourke  1 , Vandana Mridhu Sagar  1 , Tahir Shah  2 , Shishir Shetty  1
Affiliations
Review

Carcinogenesis on the background of liver fibrosis: Implications for the management of hepatocellular cancer

Joanne Marie O'Rourke et al. World J Gastroenterol. .

Abstract

Hepatocellular carcinoma (HCC) is now the second leading cause of cancer-related deaths globally and many patients have incurable disease. HCC predominantly occurs in the setting of liver cirrhosis and is a paradigm for inflammation-induced cancer. The causes of chronic liver disease promote the development of transformed or premalignant hepatocytes and predisposes to the development of HCC. For HCC to grow and progress it is now clear that it requires an immunosuppressive niche within the fibrogenic microenvironment of cirrhosis. The rationale for targeting this immunosuppression is supported by responses seen in recent trials with checkpoint inhibitors. With the impact of immunotherapy, HCC progression may be delayed and long term durable responses may be seen. This makes the management of the underlying liver cirrhosis in HCC even more crucial as studies demonstrate that measures of liver function are a major prognostic factor in HCC. In this review, we discuss the development of cancer in the setting of liver inflammation and fibrosis, reviewing the microenvironment that leads to this tumourigenic climate and the implications this has for patient management.

Keywords: Carcinogenesis; Fibrosis; Hepatocellular cancer; Immunotherapy; Inflammation.

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Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest.

Figures

Figure 1
Figure 1
Overview of the key factors associated with fibrosis development and progression to hepatocellular carcinoma. Hepatotoxic agents damage key liver cells triggering reactive oxygen species and cytokine release culminating in hepatic stellate cell activation, the key step in fibrosis development. Chronic inflammation and fibrosis instigates several changes in the microenvironment predisposing to hepatocellular carcinoma (HCC) and creating distinct immune changes which promote HCC progression. Key therapeutic strategies are highlighted in red. LSEC: Liver sinusoidal endothelial cells; KC: Kupffer cells; ROS: Reactive oxygen species; HCC: Hepatocellular carcinoma; TGFβ: Transforming growth factor β; PDGF: Platelet-derived growth factor; HSC: Hepatic stellate cell; ECM: Extracellular matrix; PV: Portal vein; LPS: Lipopolysaccharides; IL: Interleukins; Treg: Regulatory T cell; MDSC: Myeloid-derived suppressor cells; NK: Natural killer cells.
Figure 2
Figure 2
Formula to calculate the ALBI-score and translate the result to ALBI grade[64].
See this image and copyright information in PMC

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