A study of circulating interleukin 10 in prognostication of unresectable hepatocellular carcinoma.
ABSTRACT The level of circulating interleukin 10 (IL-10) is elevated in a proportion of patients with hepatocellular carcinoma (HCC). The objective of the current study was to evaluate the prognostic significance of serum the IL-10 level in patients with unresectable HCC.
Patients with unresectable HCC who provided serum at the time of diagnosis were enrolled prospectively in the study. The level of circulating IL-10 in serum samples was determined by enzyme-linked immunosorbent assay. The association of the IL-10 level with overall survival was evaluated in relation to sociodemographics, liver function, hepatitis B viral load, and tumor staging.
In total, 222 patients were recruited; of these, 82.4% were positive for hepatitis B virus surface antigen, and 65.8% had Barcelona Clinic Liver Cancer stage C disease. The mean log IL-10 level was 1.1 pg/mL, and 146 patients had an IL-10 level >1 pg/mL (high IL-10 group). The high IL-10 group had worse overall survival than the low IL-10 group (5.0 months vs 14.9 months; hazard ratio, 2.192; P < .0001). The IL-10 level was associated with worse hepatic function and with a high alanine transaminase (ALT) level. The IL-10 level remained an independent prognostic factor (hazard ratio, 1.824; P = .0005) after adjustment for sociodemographics, tumor staging, treatment, Child-Pugh stage, and ALT level. The IL-10 level also subdivided patients into 2 populations with distinct survival (10.2 months vs 3.5 months; P = .0027).
The serum IL-10 level was identified as an independent prognostic factor for unresectable HCC. The current findings suggested that an elevated IL-10 level may be related to hepatic injury caused by cirrhotic processes rather than tumor load. The authors concluded that the IL-10 level offers additional prognostic value to the existing tumor staging systems.
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ABSTRACT: Cytokine balance may play an important role in effective antiviral immunity. We determined the frequencies of interferon-gamma (IFN-gamma)-, interleukin-4 (IL-4)-, and interleukin-10 (IL-10)-secreting cells in response to HBV antigens in peripheral blood mononuclear cells (PBMCs) and liver-infiltrating lymphocytes (LILs) using an enzyme-linked immuno spot (ELISpot) assay and related them to serum ALT and HBV DNA levels, and hepatic histological findings. PBMCs were obtained from 25 patients with chronic hepatitis B, from eight of whom LILs were also obtained, and 12 healthy controls. On stimulation with hepatitis B core antigen (HBcAg), the median (range) frequencies of IFN-gamma- and IL-10-secreting cells were 25 (7-71) and 54 (26-101) cells/10(4) PBMCs, respectively, in patients with chronic hepatitis B, and 4 (0-12) and 36 (7-63) cells/10(4) PBMCs, respectively, in healthy controls. The frequencies of HBcAg-specific IFN-gamma-secreting cells in PBMCs and LILs of chronic hepatitis B patients correlated with serum ALT levels. Those of LILs correlated with serum ALT levels and HAI scores. In conclusion, HBcAg-specific IFN-gamma-secreting cells may play a role in liver damage in chronic HBV infection. Excessive IL-10 production by PBMCs and LILs in response to HBcAg may suppress antiviral immune responses and contribute to persistent infection.Hepatology Research 11/2003; 27(2):109-116. · 2.07 Impact Factor
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ABSTRACT: Preferential production of immunoregulatory cytokines may play an important role in the pathogenesis of chronic hepatitis B. We aimed to determine the serum levels of IL-2, IL-10 and TNF-alpha in patients with chronic hepatitis B and to correlate these findings with the activity of liver disease, HBeAg/anti-HBe status and replication level of the virus. Seventy-two chronic hepatitis B patients were categorized into 4 groups according to activity of liver disease and HBeAg status. Group 1 (n = 13): HBeAg and HBV DNA-positive with persistently normal ALT. Group 2 (n = 20): HBeAg and HBV DNA-positive patients with persistently elevated ALT. Group 3 (n = 19): HBeAg and HBV DNA-negative patients with persistently normal ALT. Group 4 (n = 20): HBeAg-negative patients with persistently elevated ALT and variable serum HBV DNA. IL-2, IL-10 and TNFa levels were determined in stored patient sera. Apart from group 1 patients, all patients groups had higher IL-2 levels compared to controls suggesting that IL-2 production is increased when liver disease becomes active in HBeAg-positive phase of HBV infection. Only group 2 patients had elevated IL-10 levels compared to controls. None of the HBeAg-negative patients had detectable TNF-alpha levels while 64% HBeAg-positive patients had elevated levels of TNF-alpha irrespective of the activity of liver disease. Except TNF-alpha, no association was found between HBV DNA status and the presence or absence of detectable cytokines in circulation. Our results suggest that circulating cytokine profile in chronic hepatitis B is related with the HBeAg status, replication level of the virus and the activity of liver disease.Hepato-gastroenterology 47(36):1675-9. · 0.77 Impact Factor
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ABSTRACT: A new staging system for hepatocellular carcinoma (HCC) has recently been reported from Italy (CLIP classification). It combines Child-Pugh staging with tumour criteria: tumour morphology, portal invasion, and alpha fetoprotein levels. To validate the use of the CLIP staging in a cohort of HCC patients and compare it with Okuda staging. A retrospective analysis of patients with HCC diagnosed in the Toronto General Hospital between October 1994 and December 1998. A total of 313 patients were identified; 19 patient with insufficient data and 37 transplant patients were excluded. Hence 257 patients in whom complete data for clinical staging were available were included in the study. The median survival of the cohort was 22.8 months. The CLIP stage 0 group (23.1% of the cohort) and the Okuda stage 1 group (50.7% of the cohort) had a five year survival rate of 67% and 35%, respectively (p<0.02). The CLIP stage 0 criteria more accurately defined patients with a good prognosis. The Okuda classification failed to identify two thirds of the 37 patients with a poor prognosis, who were identified by the CLIP criteria. Patients with a CLIP score > or =4 shared a very poor prognosis (median survival 1-3 months). Further classification above stage 4 was unnecessary. The CLIP classification for HCC is easy to implement and more accurate than the Okuda classification. Our cohort was different from the CLIP cohort (more hepatitis B) but the results were still consistent.Gut 06/2002; 50(6):881-5. · 10.73 Impact Factor