Decoding the hepatic fibrosis-hepatocellular carcinoma axis: from mechanisms to therapeutic opportunities

Harris R, Harman DJ, Card TR, Aithal GP, Guha IN. Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review. Lancet Gastroenterol Hepatol. 2017;2:288–297

Article  PubMed  Google Scholar 

Kim HY, Yu JH, Chon YE, Kim SU, Kim MN, Han JW, et al. Prevalence of clinically significant liver fibrosis in the general population: a systematic review and meta-analysis. Clin Mol Hepatol. 2024;30:S199-213

Article  PubMed  PubMed Central  Google Scholar 

Arnett A, Siegel DA, Dai S, Thompson TD, Foster J, di Pierro EJ, et al. Incidence and survival of pediatric and adult hepatocellular carcinoma, United States, 2001–2020. Cancer Epidemiol. 2024;92: 102610

Article  PubMed  Google Scholar 

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–263

Article  PubMed  Google Scholar 

El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–1127

Article  PubMed  CAS  Google Scholar 

Fattovich G, Giustina G, Schalm SW, Hadziyannis S, Sanchez-Tapias J, Almasio P, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The EUROHEP Study Group on Hepatitis B Virus and Cirrhosis. Hepatol Baltim Md. 1995;21:77–82

CAS  Google Scholar 

Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127:S35-50

Article  PubMed  Google Scholar 

Flemming JA, Yang JD, Vittinghoff E, Kim WR, Terrault NA. Risk prediction of hepatocellular carcinoma in patients with cirrhosis: the ADRESS-HCC risk model. Cancer. 2014;120:3485–3493

Article  PubMed  Google Scholar 

Chavda V, Zajac KK, Gunn JL, Balar P, Khadela A, Vaghela D, et al. Ethnic differences in hepatocellular carcinoma prevalence and therapeutic outcomes. Cancer Rep Hoboken NJ. 2023;6(Suppl 1): e1821

Article  Google Scholar 

Liu L, Xie Y, Yang H, Lin A, Dong M, Wang H, et al. HPVTIMER: a shiny web application for tumor immune estimation in human papillomavirus-associated cancers. iMeta. 2023;2:e130

Article  PubMed  PubMed Central  CAS  Google Scholar 

Subramaniyan V, Chakravarthi S, Jegasothy R, Seng WY, Fuloria NK, Fuloria S, et al. Alcohol-associated liver disease: a review on its pathophysiology, diagnosis and drug therapy. Toxicol Rep. 2021;8:376–385

Article  PubMed  PubMed Central  CAS  Google Scholar 

Allen AM, Therneau TM, Larson JJ, Coward A, Somers VK, Kamath PS. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: a 20 year-community study. Hepatol Baltim Md. 2018;67:1726–1736

Article  CAS  Google Scholar 

White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2012;10:1342-1359.e2

Google Scholar 

Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129:113–121

Article  PubMed  Google Scholar 

Correia AL, Guimaraes JC, Auf der Maur P, De Silva D, Trefny MP, Okamoto R, et al. Author correction: hepatic stellate cells suppress NK cell-sustained breast cancer dormancy. Nature. 2021;600:E7

Article  PubMed  CAS  Google Scholar 

Kostallari E, Wei B, Sicard D, Li J, Cooper SA, Gao J, et al. Stiffness is associated with hepatic stellate cell heterogeneity during liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2022;322:G234–G246

Article  PubMed  CAS  Google Scholar 

Lai KKY, Shang S, Lohia N, Booth GC, Masse DJ, Fausto N, et al. Extracellular matrix dynamics in hepatocarcinogenesis: a comparative proteomics study of PDGFC transgenic and Pten null mouse models. PLoS Genet. 2011;7: e1002147

Article  PubMed  PubMed Central  CAS  Google Scholar 

Wu B, Liu D-A, Guan L, Myint PK, Chin L, Dang H, et al. Stiff matrix induces exosome secretion to promote tumour growth. Nat Cell Biol. 2023;25:415–424

Article  PubMed  PubMed Central  CAS  Google Scholar 

Zhang P-C, Liu X, Li M-M, Ma Y-Y, Sun H-T, Tian X-Y, et al. AT-533, a novel Hsp90 inhibitor, inhibits breast cancer growth and HIF-1α/VEGF/VEGFR-2-mediated angiogenesis in vitro and in vivo. Biochem Pharmacol. 2020;172: 113771

Article  PubMed  CAS  Google Scholar 

Yin C-L, Ma Y-J. The regulatory mechanism of hypoxia-inducible factor 1 and its clinical significance. Curr Mol Pharmacol. 2024;17: e18761429266116

Article  PubMed  CAS  Google Scholar 

Peng S, Lin A, Jiang A, Zhang C, Zhang J, Cheng Q, et al. CTLs heterogeneity and plasticity: implications for cancer immunotherapy. Mol Cancer. 2024;23:58

Article  PubMed  PubMed Central  CAS  Google Scholar 

O’Rourke JM, Sagar VM, Shah T, Shetty S. Carcinogenesis on the background of liver fibrosis: implications for the management of hepatocellular cancer. World J Gastroenterol. 2018;24:4436–4447

Article  PubMed  PubMed Central  Google Scholar 

Li M, Huang F, Zhu W, Peng Y, Xu F, Li W, et al. Dynamic regulation of EXO1 promotes the progression from liver fibrosis to HCC through TGF-β1/Smad signaling feedback loop. Hepatol Commun. 2024;8: e0342

Article  PubMed  Google Scholar 

Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, et al. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature. 2004;431:461–466

Article  PubMed  CAS  Google Scholar 

Ramakrishna G, Rastogi A, Trehanpati N, Sen B, Khosla R, Sarin SK. From cirrhosis to hepatocellular carcinoma: new molecular insights on inflammation and cellular senescence. Liver Cancer. 2013;2:367–383

Article  PubMed  PubMed Central  CAS  Google Scholar 

Zhou Y, Zhang L, Ma Y, Xie L, Yang Y-Y, Jin C, et al. Secretome of senescent hepatic stellate cells favors malignant transformation from nonalcoholic steatohepatitis-fibrotic progression to hepatocellular carcinoma. Theranostics. 2023;13:4430–4448

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kurokawa S, Kobori T, Yoneda M, Ogawa Y, Honda Y, Kessoku T, et al. Identification of differentially methylated regions associated with both liver fibrosis and hepatocellular carcinoma. BMC Gastroenterol. 2024;24:57

Article  PubMed  PubMed Central  CAS  Google Scholar 

Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16:203–222

Article  PubMed  CAS  Google Scholar 

Wilson CL, Mann DA, Borthwick LA. Epigenetic reprogramming in liver fibrosis and cancer. Adv Drug Deliv Rev. 2017;121:124–132

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shan L, Wang F, Xue W, Zhai D, Liu J, Lv X. New insights into fibrotic signaling in hepatocellular carcinoma. Front Oncol. 2023;13:1196298

Article  PubMed  PubMed Central  CAS  Google Scholar 

Gao J, Wang Z, Wang G-J, Gao N, Li J, Zhang Y-F, et al. From hepatofibrosis to hepatocarcinogenesis: higher cytochrome P450 2E1 activity is a potential risk factor. Mol Carcinog. 2018;57:1371–1382

Article  PubMed  CAS  Google Scholar 

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