Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases—meta‐analytic assessment

Tarao, Kazuo; Nozaki, Akira; Ikeda, Takaaki; Satô, Akira; Komatsu, Hirokazu; Komatsu, Tatsuji; Taguri, Masataka; Tanaka, Katsuaki

doi:10.1002/cam4.1998

Cited by 128 publications

(111 citation statements)

References 132 publications

(153 reference statements)

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“…Although cirrhosis may be regarded as a premalignant stage, the development of HCC in cirrhosis requires additional and progressive preneoplastic stages as additional stepping stones towards HCC. 18 This spectrum of development can be crudely broken down into distinct stepwise progression events from injured, often cirrhotic, liver to focal patches of low-grade dysplastic nodules, then through high-grade dysplastic nodules onto HCC 19 (Fig. 1).…”

Section: General Concepts Surrounding the Mutational Events Leading Tmentioning

confidence: 99%

The landscape of gene mutations in cirrhosis and hepatocellular carcinoma

Müller

Bird

Nault

2020

Journal of Hepatology

124

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Chronic liver disease and primary liver cancer are a massive global problem, with a future increase in incidences predicted. The most prevalent form of primary liver cancer, hepatocellular carcinoma, occurs after years of chronic liver disease. Mutations in the genome are a causative and defining feature of all cancers. Chronic liver disease, mostly at the cirrhotic stage, causes the accumulation of progressive mutations which can drive cancer development. Within the liver, a Darwinian process selects out dominant clones with selected driver mutations but also leaves a trail of passenger mutations which can be used to track the evolution of a tumour. Understanding what causes specific mutations and how they combine with one another to form cancer is a question at the heart of understanding, preventing and tackling liver cancer. Herein, we review the landscape of gene mutations in cirrhosis, especially those paving the way toward hepatocellular carcinoma development, that have been characterised by recent studies capitalising on technological advances in genomic sequencing. With these insights, we are beginning to understand how cancers form in the liver, particularly on the background of chronic liver disease. This knowledge may soon lead to breakthroughs in the way we detect, diagnose and treat this devastating disease.

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Section: General Concepts Surrounding the Mutational Events Leading Tmentioning

confidence: 99%

The landscape of gene mutations in cirrhosis and hepatocellular carcinoma

Müller

Bird

Nault

2020

Journal of Hepatology

124

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“…Studies have reported that 80–90% of patients with HCC present liver fibrosis or cirrhosis (El-Serag, 2011). A recent meta-analysis of studies in cirrhotic patients with five liver diseases (hepatitis B, hepatitis C, primary biliary cholangitis, autoimmune hepatitis, and non-alcoholic steatohepatitis) showed that the incidence of liver cancer is significantly increased when liver disease develops into cirrhosis, indicating that cirrhosis is one of the crucial risk factors for HCC (Tarao et al, 2019). Patients with liver cancer, with or without cirrhosis, show different clinical characteristics, including differences in tumor size and prognostic factors (Techathuvanan et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel four-lncRNA signature as a prognostic indicator in cirrhotic hepatocellular carcinoma

Deng

2019

PeerJ

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Background Many studies have shown that long noncoding RNAs (lncRNA) are closely associated with the occurrence and development of various tumors and have the potential to be prognostic markers. Moreover, cirrhosis is an important prognostic risk factors in patients with liver cancer. Some studies have reported that lncRNA-related prognostic models have been used to predict overall survival (OS) and recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC). However, no one has constructed a prognostic lncRNA model only in patients with cirrhotic HCC. Thus, it is necessary to screen novel potential lncRNA markers for improve the prognosis of cirrhotic HCC patients. Methods The probe expression profile dataset (GSE14520–GPL3921) from the Gene Expression Omnibus (GEO), which included 204 cirrhotic HCC samples, was reannotated and the lncRNA and mRNA expression dataset was obtained. The patients were randomly assigned to either the training set (n = 103) and testing set (n = 100). Univariate cox regression and the least absolute shrinkage and selection operator (LASSO) model were applied to screen lncRNAs linked to the OS of cirrhotic HCC in the training set. The lncRNAs having significant correlation with OS were then selected and the multivariate Cox regression model was implemented to construct the prognostic score model. Whether or not this model was related to RFS in the training set was simultaneously determined. The testing set was used to validate the lncRNA risk score model. A risk score based on the lncRNA signature was used for stratified analysis of different clinical features to test their prognostic performance. The prognostic lncRNA-related protein genes were identified by the co-expression matrix of lncRNA-mRNA, and the function of these lncRNAs was predicted through the enrichment of these co-expression genes. Results The signature consisted of four lncRNAs:AC093797.1,POLR2J4,AL121748.1 and AL162231.4. The risk model was closely correlated with the OS of cirrhotic HCC in the training cohort, with a hazard ratio (HR) of 3.650 (95% CI [1.761–7.566]) and log-rank P value of 0.0002. Moreover, this model also showed favorable prognostic significance for RFS in the training set (HR: 2.392, 95% CI [1.374–4.164], log-rank P = 0.0015). The predictive performance of the four-lncRNA model for OS and RFS was verified in the testing set. Furthermore, the results of stratified analysis revealed that the four-lncRNA model was an independent factor in the prediction of OS and RFS of patients with clinical characteristics such as TNM (Tumor, Node, Metastasis system) stages I–II, Barcelona Clinic Liver Cancer (BCLC) stages 0–A, and solitary tumors in both the training set and testing set. The results of functional prediction showed that four lncRNAs may be potentially involve in multiple metabolic processes, such as amino acid, lipid, and glucose metabolism in cirrhotic HCC.

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“…Cirrhosis can result in jaundice, asterixis, portal hypertension (leading to portocaval anastomoses such as esophageal varices, which are the most common acute cause of death), encephalopathy, and thrombocytopenia [ 11 ]. End-stage cirrhosis requires liver transplantation for survival and also increases the risk of HCC development by 45-fold (discussed further under “risk of progression”) [ 12 ].…”

Section: Histological Progressionmentioning

confidence: 99%

Epidemiology of non-alcoholic fatty liver disease and risk of hepatocellular carcinoma progression

Thandra¹,

Barsouk²,

Saginala³

et al. 2020

ceh

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Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Its incidence has grown alongside the increasing global prevalence of type 2 diabetes, obesity, and metabolic syndrome. The risk of progression to hepatocellular carcinoma for nonalcoholic steatohepatitis patients over 5 years is 8%, and despite targeted and immunotherapy treatment advances, HCC maintains a bleak 5-year survival of 19%. NAFLD's primary risk factors are components of metabolic syndrome as well as possible sleep disturbances. NAFLD is most common among men 50-60 years of age, though incidence in women catches up after menopause. In the US, Hispanics are most likely to develop NAFLD and African Americans least likely, in part due to the prevalence of the PNPLA3 gene variant. With NAFLD risk factors especially prevalent in underserved populations and developing nations, public health interventions, earlier diagnosis, and novel treatments could curb the growing disease burden.

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Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases—meta‐analytic assessment

Cited by 128 publications

References 132 publications

The landscape of gene mutations in cirrhosis and hepatocellular carcinoma

The landscape of gene mutations in cirrhosis and hepatocellular carcinoma

Identification of a novel four-lncRNA signature as a prognostic indicator in cirrhotic hepatocellular carcinoma

Epidemiology of non-alcoholic fatty liver disease and risk of hepatocellular carcinoma progression

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