Plasma osteopontin is a biomarker for the severity of alcoholic liver cirrhosis, not for hepatocellular carcinoma screening

Abstract

BackgroundImplementation of surveillance programs for at-risk populations and identification of biomarkers for early hepatocellular carcinoma (HCC) detection are a major public health goal. Recently, osteopontin (OPN) has attracted attention as a promising biomarker, with some potential advantages compared to alpha-fetoprotein (AFP), but its role in the context of alcoholic cirrhosis has never been assessed. The aims of this study are to assess the utility of plasma OPN in the diagnosis of HCC in alcoholic cirrhotic patients and to investigate whether increased values are due to the tumor or underlying liver disease severity.MethodsA total of 90 consecutively alcoholic cirrhosis patients, observed between Jun 2013 and May 2014 at a Liver Disease Unit, were included and divided into two groups: 45 without (group I) and 45 with HCC (group II). Plasma levels of OPN (ELISA, Immuno-Biological Laboratories, Gunma, Japan) and AFP (IMMULITE® 2000 AFP, Siemens Healthcare Diagnostics, Tarrytown, New York) were assessed. The diagnostic accuracy of each marker was evaluated using Receiver-Operating Characteristic (ROC) curve analysis (AUC) and its 95 % Confidence Interval (CI).ResultsPlasma OPN levels in group I patients (1176.28 +/–744.59 ng/mL) weren’t significantly different from those of group II (1210.75 +/–800.60 ng/mL) (p = 0.826). OPN levels significantly increased with advancing BCLC tumor stage and with advancing Child-Pugh class, in both groups. Comparing the two groups, AUC for OPN and AFP were 0.51 (95 % CI: 0.39–0.63) and 0.79 (95 % CI: 0.70–0.89), respectively. Based on the ROC analysis, there were no satisfactory cut-off values for OPN that would distinguish patients with from those without tumour.ConclusionsDespite having a correlation with BCLC stage, the same was observed with progressive deterioration of underlying liver function in terms of Child-Pugh class and MELD score, and isn’t a useful diagnostic biomarker for HCC in alcoholic cirrhotic patients, particularly in the early stages. AFP confirms the performance evidenced in other studies, being superior to OPN. Searching more specific biomarkers for early diagnosis of HCC in alcoholic cirrhosis is still warranted.

Osteopontin Takes Center Stage in Chronic Liver Disease

“…( 51 ) Plasma OPN is considered a biomarker for the severity of alcohol‐associated cirrhosis and NASH‐induced cirrhosis. ( 52,53 )…”

Role of Osteopontin in Liver Diseases

“…Additionally, another study agreed that allele T/T and/or T/C rather than C/C at nt -443 not only significantly enhanced metastasis, but was also associated with overall survival and time to recurrence 75 . Other than in HCC with HBV or HCV, OPN is not a useful diagnostic marker for HCC in alcoholic cirrhotic patients, particularly in the early stages, which limits OPN to become a significant diagnostic marker for HCC 76 .…”

Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization

“…This increase in plasma OPN was attributed to increased levels TNF-α and IL-1, which are increased in inflammation and stimulate the expression of OPN. Plasma OPN also correlated with disease severity in both alcoholic liver cirrhosis and hepatic fibrosis from hepatitis C virus infection (100, 101). Moreover, hydrodynamic intravenous injection of OPN siRNA reduced liver tissue injury in a murine model of concanavalin A (ConA)-induced fulminant hepatitis (102).…”