Pathomolecular characterization of HCC in non-cirrhotic livers

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and usually arises in cirrhotic livers. Increasingly, it is diagnosed in non-cirrhotic livers. A variety of risk factors and etiologies can trigger the development of HCC in non-fibrotic and non-cirrhotic backgrounds. The most important causes are metabolic syndrome and hepatitis B virus infection. Postulated pathogenetic mechanisms are direct carcinogenesis, chronic liver injury and repair cycles, and genetic/epigenetic aberrations. Histopathology has a very important role in the diagnosis of non-cirrhotic HCC. Gross features of non-cirrhotic HCC are quite different from HCC originating in a cirrhotic background. Microscopic characteristics are similar to a classical HCC. However, certain histological variants show a predilection to occur in non-cirrhotic livers. These encompass fibrolamellar, scirrhous, steatohepatitic and mixed hepato-cholangiocarcinoma subtypes. Due to the non-cirrhotic background, adenoma, metastasis and most of the other non-neoplastic and neoplastic conditions enter the differential diagnosis. Genomic studies and morpho-molecular classifications of HCC provide further understanding of the molecular pathogenesis of non-cirrhotic HCC. This group however, has rarely been exclusively studied. This review offers an update of etiology, patho-molecular characteristics and differential diagnosis of HCC arising in non-cirrhotic backgrounds.

Non-Cirrhotic Hepatocellular Carcinoma with Duodenal Metastasis in Chronic Hepatitis B: Case Report

“…Up to 30% of HBV-related HCC arise in non-cirrhotic livers. (7) HBV is a partially double-stranded DNA virus that can integrate into the host cell and acts as a mutagenic agent causing secondary chromosomal rearrangement and increasing genomic instability or producing genotoxins such as the HBx protein, resulting in HCC development in non-cirrhotic backgrounds. (1,7,8) Transactivation of genes by the regulatory protein HBx interferes with tumorsuppressor activity through its interaction with p53.…”

“…High viral load titers (104-5 copies/mL) have been linked with PIK3CA mutations and be an independent risk factor for non-cirrhotic HCC. (7,8) Certain risk factors in chronic hepatitis B patients, in turn, impart a higher risk for noncirrhotic HCC. BCP T1762/A1764 mutation and high viral loads have been substantial viral factors and independent predictors of HCC in non-cirrhotic patients who are chronic HBV carriers.…”

Hepatocellular cancer. Current aspects of carcinogenesis

“…Изложенные современные представления о механизмах инициации, промоции и прогрессии ГЦК привели к необходимости пересмотра некоторых устоявшихся классификационных подходов к данной патологии. Эти инновации нашли отражение в нескольких фундаментальных статьях, опубликованных в последние годы [40,[57][58][59]. Квинтэссенция предлагаемых (и принятых теперь) изменений сводится к итоговой интегральной классификации ГЦК.…”

“…Суммарные различия сведены нами в таблице 3. Важно отметить, что изменения гистоструктуры опухолей также тесно связаны с дисрегуляцией молекулярных путей, мутацией генов [59]. Так, выделяют макротрабекулярный вариант ГЦК, обусловленный высокой экспрессией и мутациями гена ТР53, сосудистого эндотелиального фактора роста (VEGF) с амплификацией фибробластного фактора роста (FGF-19) [43].…”