First evaluation of Neighbor of Punc E11 (NOPE) as a novel marker in human hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide and the search for clinically useful biomarkers is ongoing. Neighbor of Punc E11 (NOPE) is an established biomarker of murine HCC that remains undetectable in normal liver and at preneoplastic stages. OBJECTIVE: The aim of our study was to evaluate the presence of NOPE in human HCC. METHODS: Histologically confirmed HCC and corresponding non-tumor liver samples from 20 patients were analyzed for expression of NOPE using qRT-PCR and mRNA-in-situ technology in a conserved tissue context. RESULTS: In our cohort, 30% of HCC samples were expressing NOPE which proved particularly useful in non-cirrhotic HCC samples with up to 155-fold higher expression than in adult liver. Using mRNA-in-situ technology, NOPE was clearly identified within epithelial tumor cells of NOPE positive human HCCs. In our analyzed cohort, the combination of AFP with NOPE did not reach more than 40% sensitivity while GPC-3 and NOPE were complementary to each other reaching a combined sensitivity of 85.7%. CONCLUSIONS: This is the first characterization of NOPE as a potential biomarker for human HCC. Our results underline the value of NOPE as a complementing biomarker for human HCC

Elevated liver fibrosis index FIB-4 is not reliable for HCC risk stratification in predominantly non-Asian CHB patients

We aimed to validate the liver fibrosis index FIB-4 as a model for risk stratification of hepatocellular carcinoma development in predominantly non-Asian patients with chronic hepatitis B infection seen at a tertiary referral center in Germany.We retrospectively analyzed 373 adult patients with chronic hepatitis B infection. Patient demographics, hepatitis B markers, antiviral treatment, laboratory parameters, results from liver imaging and histology were recorded. Patients were divided into 2 groups according to their FIB-4 levels and their hazard ratios for developing hepatocellular carcinoma were analyzed adjusted for age, sex, body mass index, alcohol consumption, and antiviral medication.Median follow-up was 8.7 years (range 1-21.3 years), 93% of patients were of non-Asian origin, and 64% were male. Compared with patients with a low FIB-4 (<1.25) patients with FIB-4 1.25 showed a hazard ratio for incidence of hepatocellular carcinoma of 3.03 (95% confidence interval (CI): 1.24-7.41) and an adjusted hazard ratio of 1.75 (95% CI: 0.64-4.74). Notably, 68% of patients with liver cirrhosis and 68% of those who developed HCC during observation had a low FIB-4 (<1.25).We could not confirm that a FIB-4 value 1.25 is a reliable clinical indicator for incidence of hepatocellular carcinoma in predominantly non-Asian patients with chronic hepatitis B. Further studies in geographically and ethnically diverse populations are needed to prove its utility as a predictive tool

CT Marker in Emergency Imaging of Acute Basilar Artery Occlusion: Thrombosis vs. Embolism

Purpose: Acute basilar artery occlusion, a neurovascular emergency leading to high rates of morbidity and mortality, is usually diagnosed by CT imaging. The outcome is partly dependent on etiology, with a worse outcome in occlusions with underlying basilar artery stenosis. As this occlusion type requires a more complex angiographic therapy, this study aimed to develop new CT markers in emergency admission imaging to rapidly identify underlying stenosis. Methods: A total of 213 consecutive patients (female n = 91, age in years (mean/SD/range): 72/13/28&ndash;97), who received endovascular treatment at a single comprehensive stroke center for acute basilar artery occlusion, were included in this study. After applying strict inclusion criteria for imaging analyses, novel CT imaging markers, such as &lsquo;absolute density loss&rsquo; (ADL) and relative thrombus attenuation (CTA-index), that measure perviousness, were assessed for n = 109 patients by use of CT-angiography and correlated to different occlusion patterns (thrombotic vs. embolic). Inter-observer agreement was assessed using an intraclass correlation coefficient for independent measures of a radiologist and a neuroradiologist. Associations between the imaging markers and clinical and interventional parameters were tested. Results: CT markers differ between the subgroups of basilar artery occlusions with and without underlying stenosis (for ADL: 169 vs. 227 HU (p = 0.03), for CTA-index: 0.55 vs. 0.70 (p &lt; 0.001)), indicating a higher perviousness in the case of stenosis. A good inter-rater agreement was observed for ADL and CTA-index measures (ICC 0.92/0.88). For the case of embolic occlusions, a more pervious thrombus correlates to shorter time intervals, longer procedure times, and worse reperfusion success (p-values &lt; 0.05, respectively). Conclusions: ADL and CTA-index are easy to assess in the emergency setting of acute basilar artery occlusion with the use of routinely acquired CT-angiography. They show a high potential to differentiate thrombotic from embolic occlusions, with an impact on therapeutic decisions and angiographic procedures. Measurements can be quickly performed with good reliability, facilitating implementation in clinical practice