Clinical course of partial virological responders under prolonged entecavir monotherapy in patients with chronic hepatitis B.

Studies about long-term entecavir (ETV) therapy for partial virological response (PVR) are lacking. This study aimed to assess the clinical course of PVR patients receiving ETV therapy and analyze the efficacy of tenofovir (TDF). We retrospectively evaluated 130 patients who showed a PVR to ETV. Among these patients, 102 were nucleot(s)ide analogue (NUC)-naïve and 28 were lamivudine (LAM)-experienced. The cumulative rates of VR were 54.1%, 70.8%, and 83.7% for the NUC-naïve group and 37.0%, 42.8%, and 42.8% for the LAM-experienced group after 24, 36, and 48 months of ETV therapy, respectively (P = 0.008). Low HBV DNA level at 12 months (P < 0.001) and absence of a LAM treatment history (P = 0.031) were significant associated factors for VR. In VR prediction at 36 months of ETV therapy in NUC-naïve patients, HBV DNA level <95 IU/ml at 12 months showed a 92.9% sensitivity and a 78.3% specificity (AUROC, 0.909; P < 0.001). ETV resistance did not develop in NUC-naïve patients with HBV DNA levels <95 IU/ml at 12 months. The cumulative probability of VR in patients who switched to or additionally received TDF was 91.3% at 15 months. Prolonged ETV therapy induced a VR without the risk of ETV resistance in NUC-naïve patients with HBV DNA levels <95 IU/ml at 12 months. All patients with LAM-experienced or NUC-naïve with HBV DNA levels ≥95 IU/ml at 12 months should be switched to TDF rescue therapy.

Interleukin-8 level as a prognostic marker in patients with hepatitis B virus-associated hepatocellular carcinoma treated with transarterial chemoembolization.

We investigated the association between serum interleukin (IL)-8 levels and post-transarterial chemoembolization (TACE) outcomes in patients with hepatitis B virus (HBV)-associated HCC. We enrolled 119 TACE-treated patients with HBV-associated HCC; TACE refractoriness and liver transplantation (LT)-free survival were evaluated during follow-up. Pre-TACE serum levels of various cytokines (epidermal growth factor [EGF], fibroblast growth factor 2, granulocyte-colony stimulating factor [G-CSF], interferon-γ, IL-8, IL-12, IL-17A, interferon-γ-inducible protein-10, monocyte chemotactic protein-1, tumor necrosis factor-α and vascular endothelial growth factor) were analyzed. During a mean follow-up of 24.3 (1-79) months, 91 patients (76.5%) exhibited TACE refractoriness. In multivariate analyses, multiple tumors (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.28-4.39; P=0.006), large tumor size (HR, 2.36; 95% CI, 1.38-4.03; P=0.002), and combination of alpha-fetoprotein and IL-8 levels (AFP>400 ng/mL or IL-8>32 pg/mL; HR, 1.72; 95% CI, 1.03-2.85; P=0.037) independently predicted overall TACE refractoriness. Higher EGF (>35 pg/mL) and lower G-CSF levels (⩽ 12.5 pg/mL) were associated with early TACE refractoriness (<1 year; HR, 3.47; 95% CI, 1.01-11.96; P=0.049 and HR, 6.25; 95% CI, 1.62-23.81; P=0.008, respectively). Furthermore, high IL-8 level (>32 pg/mL; HR, 1.68; 95% CI, 1.09-2.59; P=0.020) was associated with poor LT-free survival. In conclusion, pretreatment serum IL-8 is a useful prognostic marker for TACE refractoriness and LT-free survival in TACE-treated patients with HBV-associated HCC.

Effect of virological response to entecavir on the development of hepatocellular carcinoma in hepatitis B viral cirrhotic patients: comparison between compensated and decompensated cirrhosis.

OBJECTIVES: This study aimed to evaluate the risk of development of hepatocellular carcinoma (HCC) according to underlying liver status and virological response (VR) to entecavir (ETV) in chronic hepatitis B patients with cirrhosis. Procollagen III N-terminal peptide (PIIINP) concentration during ETV treatment and its association with HCC development were also evaluated. METHODS: A total of 306 patients with clinically diagnosed liver cirrhosis were treated with ETV for ≥12 months and were subsequently followed up for the occurrence of HCC (median follow-up duration: 37.0 months). Patients who developed HCC within 12 months were excluded. VR was defined as a hepatitis B virus DNA level <20 IU/ml at 12 months after ETV treatment. RESULTS: A total of 209 patients (68.3%) had compensated cirrhosis, and the remaining patients (31.7%) had decompensated cirrhosis. The 5-year cumulative incidence of HCC was 26.8%. A multivariate Cox regression analysis identified the following independent risk factors for developing HCC in all the patients: age >50 years (hazard ratio (HR)=8.41; 95% confidence interval (CI)=3.86-18.28; P=0.000), male sex (HR=4.24; 95% CI=1.83-9.81; P=0.001), high serum PIIINP level at 12 months (HR=1.07; 95% CI=1.02-1.13; P=0.007), and no VR at 12 months (HR=2.10; 95% CI=1.02-4.33; P=0.043). The subgroup analyses showed that no VR at 12 months is a significant risk factor for developing HCC in the patients with decompensated cirrhosis (HR=7.74; 95% CI=1.34-44.78; P=0.022) but not in those with compensated cirrhosis (P=0.749). CONCLUSIONS: The antiviral treatment with ETV did not completely eliminate the risk of developing HCC in our patients with cirrhosis. However, VR to ETV was associated with a low probability that the patients with decompensated cirrhosis would develop HCC.