MRE and SWE may have the highest diagnostic accuracy for staging fibrosis in NAFLD patients. Among the four noninvasive simple indexes, NFS and FIB-4 probably offer the best diagnostic performance for detecting AF. (Hepatology 2017;66:1486-1501).

The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (Fibrosis 4 index; FIB-4) are the two most widely studied noninvasive tools for assessing liver fibrosis. Our aims were to systematically review the performance of APRI and FIB-4 in hepatitis B virus (HBV) infection in adult patients and compare their advantages and disadvantages. We examined the diagnostic accuracy of APRI and FIB-4 for significant fibrosis, advanced fibrosis, and cirrhosis based on their sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUROC). Heterogeneity was explored using metaregression. Our systemic review and meta-analysis included 16 articles of APRI only, 21 articles of APRI and FIB-4 and two articles of FIB-4 for detecting different levels of liver fibrosis. With an APRI threshold of 0.5, 1.0, and 1.5, the sensitivity and specificity values were 70.0% and 60.0%, 50.0% and 83.0%, and 36.9% and 92.5% for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. With an FIB-4 threshold of 1.45 and 3.25, the sensitivity and specificity values were 65.4% and 73.6% and 16.2% and 95.2% for significant fibrosis. The summary AUROC values using APRI and FIB-4 for the diagnosis of significant fibrosis, advanced fibrosis, and cirrhosis were 0.7407 (95% confidence interval [CI]: 0.7033-0.7781) and 0.7844 (95% CI: 0.7450-0.8238; (Z 5 1.59, P 5 0.06), 0.7347 (95% CI: 0.6790-0.7904) and 0.8165 (95% CI: 0.7707-0.8623; Z 5 2.01, P 5 0.02), and 0.7268 (95% CI: 0.6578-0.7958) and 0.8448 (95% CI: 0.7742-0.9154; (Z 5 2.34, P 5 0.01), respectively. Conclusions: Our meta-analysis suggests that APRI and FIB-4 can identify hepatitis B-related fibrosis with a moderate sensitivity and accuracy. (HEPATOLOGY 2015;61:292-302)

Purpose: We assessed the efficacy and safety of camrelizumab [an anti-programmed death (PD-1) mAb] plus apatinib (a VEGFR-2 tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods: This nonrandomized, open-label, multicenter, phase II study enrolled patients with advanced HCC who were treatment-naïve or refractory/intolerant to first-line targeted therapy. Patients received intravenous camrelizumab 200 mg (for bodyweight ≥50 kg) or 3 mg/kg (for bodyweight <50 kg) every 2 weeks plus oral apatinib 250 mg daily. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC) per RECIST v1.1. Results: Seventy patients in the first-line setting and 120 patients in the second-line setting were enrolled. As of January 10, 2020, the ORR was 34.3% [24/70; 95% confidence interval (CI), 23.3–46.6] in the first-line and 22.5% (27/120; 95% CI, 15.4–31.0) in the second-line cohort per IRC. Median progression-free survival in both cohorts was 5.7 months (95% CI, 5.4–7.4) and 5.5 months (95% CI, 3.7–5.6), respectively. The 12-month survival rate was 74.7% (95% CI, 62.5–83.5) and 68.2% (95% CI, 59.0–75.7), respectively. Grade ≥3 treatment-related adverse events (TRAE) were reported in 147 (77.4%) of 190 patients, with the most common being hypertension (34.2%). Serious TRAEs occurred in 55 (28.9%) patients. Two (1.1%) treatment-related deaths occurred. Conclusions: Camrelizumab combined with apatinib showed promising efficacy and manageable safety in patients with advanced HCC in both the first-line and second-line setting. It might represent a novel treatment option for these patients. See related commentary by Pinato et al., p. 908

BackgroundHepatocellular carcinoma (HCC) is associated with inflammation, and roughly 30 % of the global population shows serological evidence of current or past infection with hepatitis B or hepatitis C virus. Resident hepatic macrophages, known as Kupffer cells (KCs), are considered as the specific tumor-associated macrophages (TAMs) of HCC, and can produce various cytokines—most importantly interleukin (IL)-6—to promote tumorigenesis of HCC. However, the roles of KCs and IL-6 in carcinogenesis in the liver are still unclear.MethodsWe analyzed leukocyte-related peripheral blood data of 192 patients and constructed a mouse model in which the bone marrow was cleared out by irradiation and reconstructed using bone marrow donated from IL-6-deficient mice to further elucidate the hepatic pathological changes in response to toxic challenge and oncogenic gene mutation.ResultsPeripheral monocyte counts and serum IL-6 levels were significantly higher in patients with HCC than in those without HCC. In addition, there was a significant difference in the levels of IL-6 among individuals with different histopathological grades. In mice with selective IL-6 ablation in monocytes/KCs, we observed decreased toxic liver injury, inflammatory infiltration, and systemic inflammation. In Mdr2-deficient mice, which spontaneously developed HCC, the loss of IL-6 in monocytes/KCs resulted in inhibition of IL-6/signal transducer and activator of transcription 3 signaling, decreased serum IL-6 levels, and delayed tumorigenesis.ConclusionsOur findings demonstrate that increased TAM-derived IL-6 had an amplifying effect on the inflammation response, thereby promoting the occurrence and development of HCC.

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