Evaluation of serum interleukin-6 levels in hepatocellular carcinoma patients: a systematic review and meta-analysis

Abstract

Aim of the studyThis meta-analysis evaluated serum interleukin-6 (IL-6) levels in hepatocellular carcinoma (HCC) patients compared with healthy controls and hepatitis and cirrhotic patients.Material and methodsThe three databases PubMed, Scopus, and Web of Science were searched for assessment of IL-6 levels in HCC patients (without cirrhosis and hepatitis) compared with healthy controls (without HCC, cirrhosis and hepatitis) and the studies were selected based on inclusion and exclusion criteria. A random-effect meta-analysis was performed with RevMan 5.3 software, using mean difference (MD) and 95% confidence intervals (CIs).ResultsOut of 503 studies searched in databases, 18 studies were included in the meta-analysis. The pooled analysis with continuous data demonstrated that the IL-6 level in HCC patients was significantly higher than that in healthy controls (MD = 12.44; 95% CI: 9.02-15.85; p < 0.00001). Also, the pooled analysis demonstrated that the IL-6 levels in cirrhotic patients (MD = –6.98; 95% CI: –12.91-1.05; p < 0.02) and patients with hepatitis (MD = –8.43; 95% CI: –11.91-4.95; p < 0.00001) were significantly lower than the level in HCC patients, and the subgroup analyses had high heterogeneity.ConclusionsThe elevated IL-6 levels in HCC patients compared with hepatitis and cirrhosis patients and healthy controls may show a significant association of this cytokine with increased risk of HCC and its potential as a diagnostic marker for HCC in future diagnostic and therapeutic strategies.

A Non-severe Coronavirus Disease 2019 Patient With Persistently High Interleukin-6 Level

“…For our case, his clinical manifestation and imaging features, the derangement in his liver enzymes, and elevation of his AFP with reactive Hep B infection indicate the possibility of the progression to HCC. A combination of elevation of IL-6 and AFP has moderate accuracy in predicting the future HCC development in chronic hepatitis B patients ( 9 ). The limitation of this study was that liver biopsy for the confirmatory diagnosis of HCC was not done, as he had an unregistered status and financial constraint.…”

Jak-Stat Signaling Induced by Interleukin-6 Family Cytokines in Hepatocellular Carcinoma

“…Evidence for increased IL-6 levels in chronic liver diseases has already been described more than 25 years ago [76,77,78]. Most recently, a systematic review and meta-analysis confirmed elevated IL-6 serum levels in HCC patients compared to healthy controls, and showed that HCC patients had even higher IL-6 levels than patients with other chronic liver diseases like cirrhosis or hepatitis [79]. Furthermore, high IL-6 levels might be associated with poor prognosis of patients with advanced HCC [80].…”

Immunological characterization of hepatocellular carcinoma

“…Although studies have shown that IL-6 deletion reduces spontaneous carcinogenesis and delays HCC tumorigenesis, IL- 6 has not yet been exploited as a target for immunotherapy [105,106] . However, it is worth mentioning that clinical trials examining anti-hepatitis virus drugs such as telbivudine and sofosbuvir use IL-6 as a marker of therapeutic response [107,108] .…”