Clinical proteomics for liver disease: a promising approach for discovery of novel biomarkers

Hepatocellular carcinoma (HCC) is the fifth most common cancer and advanced hepatic fibrosis is a major risk factor for HCC. Hepatic fibrosis including liver cirrhosis and HCC are mainly induced by persistent hepatitis B or C virus infection, with approximately 500 million people infected with hepatitis B or C virus worldwide. Furthermore, the number of patients with non-alcoholic fatty liver disease (NAFLD) has recently increased and NAFLD can progress to cirrhosis and HCC. These chronic liver diseases are major causes of morbidity and mortality, and the identification of non-invasive biomarkers is important for early diagnosis. Recent advancements in quantitative and large-scale proteomic methods could be used to optimize the clinical application of biomarkers. Early diagnosis of HCC and assessment of the stage of hepatic fibrosis or NAFLD can also contribute to more effective therapeutic interventions and an improve prognosis. Furthermore, advancements of proteomic techniques contribute not only to the discovery of clinically useful biomarkers, but also in clarifying the molecular mechanisms of disease pathogenesis by using body fluids, such as serum, and tissue samples and cultured cells. In this review, we report recent advances in quantitative proteomics and several findings focused on liver diseases, including HCC, NAFLD, hepatic fibrosis and hepatitis B or C virus infections

Highly sensitive Lens culinaris agglutinin‑reactive fraction of α‑fetoprotein is a predictive marker for hepatocarcinogenesis in long‑term observation of patients with chronic liver disease

Highly sensitive Lens culinaris agglutinin‑reactive fraction of α‑fetoprotein (hs‑AFP‑L3) is a specific marker for hepatocellular carcinoma (HCC) and has been reliable in cases with a low serum α‑fetoprotein (AFP) level. However, the biomarkers that contribute to hepatocarcinogenesis during the long‑term observation are not yet clear. The present study reported the clinical utility of hs‑AFP‑L3 in the long‑term observation of patients with chronic liver disease. The subjects were 106 patients with chronic liver disease without HCC or a history of HCC treatment and who had been followed for >12 months. hs‑AFP‑L3 was measured using cryopreserved serum. The factors contributing to hepatocarcinogenesis were examined using univariate and multivariate analyses. The median observation period was 88 months (15‑132 months). The cumulative incidence of HCC was 10.5% at 5 years and 19.6% at 10 years. The univariate analysis revealed that age ≥55 years old, platelet count ≤13.1x104/µl, hyaluronic acid ≥80.8 ng/ml, alanine transaminase ≥47 U/l, AFP ≥6.3 ng/ml, hs‑AFP‑L3 ≥3.5% and des‑γ‑carboxy prothrombin (DCP) ≥25 mAU/ml were significant factors. In the multivariate analysis, platelet count ≤13.1x104/µl [hazard ratio (HR), 4.966; 95% confidence interval (CI), 1.597‑15.437; P=0.006] and hs‑AFP‑L3 ≥3.5% (HR, 5.450; 95% CI, 1.522‑19.512; P=0.009) were extracted as significant factors contributing to hepatocarcinogenesis. In addition, for cases with AFP <20 ng/ml, a multivariate analysis revealed that hs‑AFP‑L3 ≥4.9% (HR, 11.608; 95% CI, 2.422‑55.629; P=0.002) and DCP ≥25 mAU/ml (HR, 3.936; 95% CI, 1.088‑14.231; P=0.037) were significant factors contributing to hepatocarcinogenesis. hs‑AFP‑L3 is a useful marker for predicting hepatocarcinogenesis in the long‑term observation of patients with chronic liver disease. Kazuaki Tabu, Seiichi Mawatari, Kohei Oda, Ohki Taniyama, Ai Toyodome, Sho Ijuin, Haruka Sakae, Kotaro Kumagai, Shuji Kanmura, Akio Ido Highly sensitive Lens culinaris agglutinin‑reactive fraction of α‑fetoprotein is a predictive marker for hepatocarcinogenesis in long‑term observation of patients with chronic liver disease MOLECULAR AND CLINICAL ONCOLOGY 15: 174, 2021 https://doi.org/10.3892/mco.2021.233