Diagnostic usefulness of real-time elastography for liver fibrosis in chronic viral hepatitis B and C.

The aim of this study was to investigate the diagnostic usefulness of real-time elastography (RTE) for liver fibrosis in chronic viral hepatitis B (CHB) and C (CHC). Fifty-one and thirty-two of the patients were diagnosed with CHB and CHC, respectively. Enrolled patients underwent liver biopsy and RTE. The FIB-4 index and aspartate transaminase-to-platelet ratio index (APRI) were also measured. The liver fibrosis index (LFI) by RTE increased significantly with the Knodell fibrosis stage: 3.14 ± 0.62 for F0, 3.28 ± 0.42 for F1, 3.43 ± 0.53 for F3, and 4.09 ± 1.03 for F4 (P = 0.000). LFI as well as APRI, FIB-4, platelet, albumin, and prothrombin time showed the difference in patients with advanced fibrosis (≥F3) and those with mild fibrosis (≤F1). In addition, RTE had better discrimination power between ≥F3 and F4 than between FIB-4 and APRI. In CHC patients, the area under receiver operating characteristic curves of RTE for advanced fibrosis was higher than that in CHB patients (0.795 versus 0.641). RTE is useful for the assessment of advanced fibrosis in patients with CHB and CHC and has better discrimination power than other serologic markers.

Change in inflammatory cytokine profiles after transarterial chemotherapy in patients with hepatocellular carcinoma.

BACKGROUND: Alterations in cytokine profiles after chemotherapy can affect the outcomes of cancer patients. This study evaluated the clinical implications of cytokine changes after transarterial chemo-embolization (TACE) in patients with hepatocellular carcinoma (HCC). METHODS: Cytometric bead immunoassays were used to simultaneously measure 13 cytokines (interleukin [IL]-12p70, interferon-γ, IL-17A, IL-2, IL-10, IL-9, IL-22, IL-6, IL-13, IL-4, IL-5, IL-1ß, and tumor necrosis factor-α) in the sera of 83 patients with HCC and 33 healthy controls. Cytokines were serially monitored at baseline, on days 3 and 7, and 2months after TACE in 63 evaluable patients. RESULTS: Serum levels of IL-5, IL-6, and IL-17A were higher in patients with HCC than in healthy controls, whereas IL-1ß and IL-22 levels were lower in patients with HCC. Of the cytokines measured, only the IL-6 level showed a significant positive correlation with both tumor size and Child-Pugh score. The Child-Pugh B/C group had higher IL-6 and lower IL-22 levels at baseline and exhibited relatively minor changes in cytokine levels compared with the Child-Pugh A group. We observed diverse changing patterns of individual cytokines on each date tested, with IL-6 and IL-22 increasing early after TACE. Particularly, IL-6 reached a peak on day 3 and finally decreasing on and after day 7. IL-4, IL-5, and IL-10, on the other hand, increased during the late phase, 2months after TACE. Patients with larger tumors (>5cm) showed a transient but significant early-phase increase in IL-6 levels coupled with severe post-TACE hepatitis, as well as late-phase increases in IL-4, IL-5, and IL-10 levels after TACE. CONCLUSIONS: TACE induces changes in levels of multiple cytokines. Distinct panels of cytokine changes are not uniform, and are influenced by treatment-induced inflammation, underlying liver function, and HCC stage. Early-phase increases in IL-6 after TACE reflect acute-phase responses and are partly associated with post-treatment hepatitis, while late-phase increases in Th2 cytokine profiles suggest immune suppression in patients with large tumors.

Prognostic value of C-reactive protein and neutrophil-to-lymphocyte ratio in patients with hepatocellular carcinoma.

BACKGROUND: Accumulating evidence indicates that components of the systemic inflammatory response, such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis of various cancers. We aimed to elucidate whether CRP and NLR could serve as potential surrogate markers for response and survival in patients with hepatocellular carcinoma (HCC). METHODS: The study population consisted of 318 consecutive patients with HCC. CRP and NLR were measured at baseline with follow-up measurements. RESULTS: With the mean follow-up of 13.9 months, the median survival time was 13.8 months. Child-Pugh class, tumor size > 5 cm, tumor multiplicity, presence of portal vein thrombosis, α-fetoprotein > 200 ng/mL, CRP > 6.3 mg/L and NLR > 2.3 were identified as independent factors for worse survival of HCC (all p < 0.05). Patients with elevated CRP (> 6.3 mg/L) and elevated NLR (> 2.3) had a significantly shorter overall survival than those with low CRP and low NLR (all p < 0.001). The combined use of CRP and NLR provided incremental prognostic information. With significant inter-correlations, levels of CRP and NLR escalated with aggravating Child-Pugh class from A to C or progressing tumor stage from I to IV. CRP and NLR on baseline and serial measurements were well predictive of treatment response (p < 0.001). CONCLUSIONS: CRP and NLR are independent indicators for survival in HCC patients, reflecting tumor burden and hepatic reserve. Their role in predicting tumor response and survival is more enhanced when used in combination. This study suggests that CRP and NLR are important prognostic biomarkers for HCC.

Serum interleukin-6 and C-reactive protein as a prognostic indicator in hepatocellular carcinoma.

The development of hepatocellular carcinoma (HCC) is often associated with chronic inflammation, suggesting a strong relationship between inflammation and carcinogenesis. This study evaluated the prognostic values of inflammatory and T-helper (Th) cytokines in the clinical outcome and survival of HCC. The study included 110 patients with HCC undergoing loco-regional therapy and 24 healthy controls. Five Th1/Th2 cytokines and C-reactive protein (CRP) were quantified before and after loco-regional treatment, using enzyme-linked immunosorbent assays. Levels of CRP, interleukin (IL)-4, and IL-6 were higher in patients with HCC than those in healthy subjects. Tumor characteristics, Child-Pugh class, and CRP, IL-6, and IL-10 levels were associated with HCC survival (all P<0.05). With multivariate analysis, higher IL-6 levels were identified as the independent cytokine for shorter survival (P=0.010). Higher CRP and IL-6 levels correlated well with larger tumor size, poor Child-Pugh function, and shorter survival, with a significant inter-correlation (r=0.667). On serial measurements, the association of CRP with tumor response was stronger than that of α-fetoprotein or other cytokines. IL-6 and CRP are strong inflammatory indicators predictive of outcome in patients with HCC receiving loco-regional therapy. This study suggests that inflammatory activation of the IL-6/CRP network may be a potential therapeutic target and biomarker for HCC.