Serum Levels of Interleukin-10 and Interleukin-12 Predict Early, Spontaneous Hepatitis B Virus e Antigen Seroconversion

Wu, Jiafeng; Wu, Tzee–Chung; Chen, Chien‐Hung; Ni, Yen‐Hsuan; Chen, Huey–Ling; Hsu, Hong–Yuan

doi:10.1053/j.gastro.2009.09.018

Cited by 114 publications

(95 citation statements)

References 23 publications

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“…[30][31][32] Recent animal studies have shown that androgen increased HBV gene transcription, which was repressed by the estrogen pathway. [33][34][35] Serum testosterone level in chronic HBV-infected males was also associated with the severity of hepatocyte damage in our previous study.…”

Section: Discussionmentioning

confidence: 99%

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Predictors of hepatitis B e antigen‐negative hepatitis in chronic hepatitis B virus‐infected patients from childhood to adulthood

Chiu

Chang

et al. 2015

Hepatology

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Hepatitis B e antigen (HBeAg)-negative hepatitis is a clinical indicator of poor outcome for chronic hepatitis B viral (HBV) infection. This long-term prospective cohort study aimed to elucidate the predictors of developing HBeAg-negative hepatitis in chronic HBV-infected subjects followed from childhood to adulthood. We followed 434 HBeAgpositive chronic HBV-infected patients from a median age of 7.22 years (interquartile range 4.31-10.21 years). Spontaneous HBeAg seroconversion occurred in 359 subjects at a median age of 13.93 years (interquartile range 8.76-20.59 years), and 75 subjects developed HBeAg seroconversion after antiviral therapy. These patients were followed for a median of 14.40 years (interquartile range 6.14-22.02 years) after HBeAg seroconversion. Clinical data were analyzed to delineate the predictors of developing HBeAgnegative hepatitis. The HBV basal core promoter and precore/core gene sequences were also evaluated in subjects with and without HBeAg-negative hepatitis. The overall annual incidence of HBeAg-negative hepatitis was 0.37% (95% confidence internal 0.35-0.39) in spontaneous HBeAg seroconverters. The overall annual incidence of HBeAg-negative hepatitis increased to 2.64% in lamivudine-treated subjects but did not increase in those treated with interferon-alpha (0.58%). Male gender (hazard ratio 5 3.15), HBV genotype C (hazard ratio 5 4.40), HBeAg seroconversion after 18 years of age (hazard ratio 5 2.46), and lamivudine therapy prior to HBeAg seroconversion (hazard ratio 5 1.42) were predictors of HBeAg-negative hepatitis in HBeAg seroconverters (P < 0.05). HBeAg-negative hepatitis subjects carried more A1762T/G1764A, C2063A, and A2131C HBV gene mutations than those without HBeAg-negative hepatitis. Conclusions: HBeAg seroconversion during childhood predicts a lower risk of HBeAgnegative hepatitis in later life. Interferon-alpha therapy may be an effective antiviral therapy beneficial in chronic HBV-infected children with severe inflammation that facilitates HBeAg seroconversion in earlier life. (HEPATOLOGY 2016;63:74-82)

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Section: Discussionmentioning

confidence: 99%

“…seroconversion at [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][30][31][32][33][34][35][36][37][38][39][40], and >40 years of age, respectively. 5,6 These differences may be attributable to differences in the studied cohorts.…”

Section: Discussionmentioning

confidence: 99%

Predictors of hepatitis B e antigen‐negative hepatitis in chronic hepatitis B virus‐infected patients from childhood to adulthood

Chiu

Chang

et al. 2015

Hepatology

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“…IL-10 acts as a repressor in liver regeneration via limiting inflammatory cytokine response and subsequently tempering hepatic STAT3 activation. Elevated levels of serum and hepatic IL-10 have been found in patients with various liver diseases, 34,35 which may play an important role not only in reducing liver inflammation but also in tempering liver over-regeneration stimulated by inflammatory response without causing liver tumor transformation.…”

Section: Il-10 Negatively Regulates Hepatocyte Proliferation and Livementioning

confidence: 99%

Enhanced Liver Regeneration in IL-10–Deficient Mice after Partial Hepatectomy via Stimulating Inflammatory Response and Activating Hepatocyte STAT3

Yin

Wang

Park

et al. 2011

The American Journal of Pathology

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Emerging evidence suggests that proinflammatory cytokines, including tumor necrosis factor-␣ (TNF-␣) and interleukin-6 (IL-6), play a critical role in the initiation and progression of liver regeneration; however, relatively little is known about the role of antiinflammatory cytokine IL-10 in liver regeneration after partial hepatectomy (PHx). Here, we examined the role of IL-10 in liver regeneration using a model of PHx in several strains of genetically modified mice. After PHx, expression of IL-10 mRNA in the liver and spleen was significantly elevated. Such elevation was diminished in TLR4 mutant mice. Compared with wild-type mice, IL-10 ؊/؊ mice had higher levels of expression of proinflammatory cytokines (IL-6, TNF-␣, and IFN-␥) and inflammatory markers (CCR2 and F4/80) in the liver, as well as higher serum levels of proinflammatory cytokines after PHx. The number of neutrophils and macrophages was also higher in the livers of IL-10 ؊/؊ mice than in wild-type mice after PHx. Liver regeneration as determined by BrdU incorporation after PHx was higher in IL-10 ؊/؊ mice than in wild-type mice, which was associated with higher levels of activation of IL-6 downstream signal STAT3 in the liver. An additional deletion of STAT3 in hepatocytes significantly reduced liver regeneration in IL-10 ؊/؊ mice after PHx. Collectively, IL-10 plays an important role in negatively regulating liver regeneration via limiting inflammatory response and subsequently tempering hepatic STAT3 activation.

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“…14 It has been suggested that IL-10 is involved in viral-related inflammation in the liver, [15][16][17] and circulating IL-10 is detected in a proportion of patients with HCC. [18][19][20] In patients with resectable HCC, a surgical series reported that an IL-10 level >12 pg/mL was associated with a worse postoperative outcome.…”

Section: Introductionmentioning

confidence: 99%

A study of circulating interleukin 10 in prognostication of unresectable hepatocellular carcinoma

Chan

Wong

et al. 2011

Cancer

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BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. Cancer 2012. © 2011 American Cancer Society.

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Serum Levels of Interleukin-10 and Interleukin-12 Predict Early, Spontaneous Hepatitis B Virus e Antigen Seroconversion

Cited by 114 publications

References 23 publications

Predictors of hepatitis B e antigen‐negative hepatitis in chronic hepatitis B virus‐infected patients from childhood to adulthood

Predictors of hepatitis B e antigen‐negative hepatitis in chronic hepatitis B virus‐infected patients from childhood to adulthood

Enhanced Liver Regeneration in IL-10–Deficient Mice after Partial Hepatectomy via Stimulating Inflammatory Response and Activating Hepatocyte STAT3

A study of circulating interleukin 10 in prognostication of unresectable hepatocellular carcinoma

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