Metabolized by liver sinusoidal endothelial cells, autotaxin (ATX) is a secreted enzyme considered to be associated with liver damage. We sought to clarify the diagnostic ability of ATX for liver fibrosis in 593 biopsy-confirmed hepatitis C virus (HCV)-infected patients. The diagnostic accuracy of ATX was compared with clinical parameters and the established fibrosis biomarkers Wisteria floribunda agglutinin-positive Mac-2-binding protein, FIB-4 index, AST-to-platelet ratio, and Forn’s index. Median ATX levels were consistently higher in female controls and patients than in their male counterparts (P < 0.01). Serum ATX concentration increased significantly according to liver fibrosis stage in overall and both genders (P < 0.001). The cutoff values of ATX for prediction of fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 0.8, 1.1, 1.3, and 1.7 mg/L, respectively, in male patients and 0.9, 1.7, 1.8, and 2.0 mg/L, respectively, in female patients. The area under the receiver operating characteristic curve for ATX to diagnose fibrosis of ≥F2 (0.861) in male patients was superior to those of FIB-4 index and Forn’s index (P < 0.001), while that in female patients (0.801) was comparable with those of the other markers. ATX therefore represents a novel non-invasive biomarker for liver fibrosis in HCV-infected patients.

AIMThe impact of mild drinking habit (less than 20 g/d of ethanol) on the clinical course of non-alcoholic fatty liver disease (NAFLD) has not been determined. We examined the influence of a mild drinking habit on liver carcinogenesis from NAFLD.METHODSA total of 301 patients who had been diagnosed as having NAFLD by liver biopsy between 2003 and 2016 [median age: 56 years, 45% male, 56% with non-alcoholic steatohepatitis, 26% with advanced fibrosis (F3-4)] were divided into the mild drinking group with ethanol consumption of less than 20 g/d (mild drinking group, n = 93) and the non-drinking group (n = 208). Clinicopathological features at the time of liver biopsy and factors related to hepatocellular carcinoma (HCC) occurrence were compared between the groups.RESULTSWe observed significant differences in male prevalence (P = 0.01), platelet count (P = 0.04), and gamma-glutamyl transpeptidase (P = 0.02) between the test groups. Over 6 years of observation, the HCC appearance rate was significantly higher in the mild drinking group (6.5% vs 1.4%, P = 0.02). Multivariate survival analysis using Cox’s regression model revealed that hepatic advanced fibrosis (F3-4) (P < 0.01, risk ratio: 11.60), diabetes mellitus (P < 0.01, risk ratio: 89.50), and serum triglyceride (P = 0.04, risk ratio: 0.98) were factors significantly related to HCC in all NAFLD patients, while the effect of a drinking habit was marginal (P = 0.07, risk ratio: 4.43). In patients with advanced fibrosis (F3-4), however, a drinking habit (P = 0.04, risk ratio: 4.83), alpha-fetoprotein (P = 0.01, risk ratio: 1.23), and diabetes mellitus (P = 0.03, risk ratio: 12.00) were identified as significant contributors to HCC occurrence.CONCLUSIONA mild drinking habit appears to be a risk factor for hepatocarcinogenesis in NAFLD patients, especially those with advanced fibrosis.

Aim Serum glycosylated Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+‐M2BP) is a reliable, non‐invasive marker of liver fibrosis. This study assessed the ability of WFA+‐M2BP to diagnose liver fibrosis in patients with chronic hepatitis B virus (HBV) infection and evaluated WFA+‐M2BP as a predictor of hepatocellular carcinoma (HCC) development. Methods Serum WFA+‐M2BP values were retrospectively evaluated in 112 treatment‐naïve patients with HBV‐related chronic hepatitis and cirrhosis who had undergone liver biopsy at our hospital. Results Serum WFA+‐M2BP levels were significantly related with liver fibrosis (r = 0.3725, P = 0.001). Fibrosis stage F2, F3, and F4 had a cut‐off index of 0.94, 1.26, and 1.26, respectively. For diagnosing F ≥ 2 fibrosis, the area under the receiver–operating characteristic curve for WFA+‐M2BP was 0.713 and comparable with those of other non‐invasive fibrosis markers, such as hyaluronic acid, type IV collagen 7S, aspartate aminotransferase‐to‐platelet ratio index, fibrosis‐4 index, serum albumin, and platelet count. Multivariate analysis identified male, WFA+‐M2BP ≥0.71, alanine aminotransferase ≥80 IU/L, and platelet count <14.5 × 109/L as independent risk factors for the development of HCC in patients with HBV infection. Conclusions Serum WFA+‐M2BP values appear to be useful for assessing liver fibrosis stage and are independently associated with HCC development in patients with chronic HBV infection.

AIMTo examine the relationship between serum autotaxin (ATX) concentrations and clinicopathological findings in non-alcoholic fatty liver disease (NAFLD) patients.METHODSOne hundred eighty-six NAFLD patients who had undergone liver biopsy between 2008 and 2017 were retrospectively enrolled. Serum samples were collected at the time of biopsy and ATX was measured by enzyme immunoassays. Sera obtained from 160 healthy, non-obese individuals were used as controls. Histological findings were graded according to an NAFLD scoring system and correlations with serum ATX were calculated by Spearman’s test. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). Cut-off values were identified by the Youden index, and the nearest clinically applicable value to the cutoff was considered the optimal threshold for clinical convenience.RESULTSSerum ATX levels were significantly higher in NAFLD patients than in controls (0.86 mg/L vs 0.76 mg/L, P < 0.001) and correlated significantly with ballooning score and fibrosis stage (r = 0.36, P < 0.001 and r = 0.45, P < 0.001, respectively). Such tendencies were stronger in female patients. There were no remarkable relationships between ATX and serum alanine aminotransferase, lipid profiles, or steatosis scores. The AUC values of ATX for predicting the presence of fibrosis (≥ F1), significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4), were all more than 0.70 in respective analyses.CONCLUSIONSerum ATX levels may at least partially reflect histological severity in NAFLD.

Background: Cerebral microbleeds (MBs) have been well investigated in Alzheimer's disease (AD), but not very extensively in non-AD dementias or in dementia with Lewy bodies (DLB). Aims: To elucidate the clinical significance of MBs in DLB. Methods: We compared the prevalence, locations and risk factors for MBs in 59 DLB and 81 AD patients. We visually counted MBs in each of the cortical and subjacent areas (frontal, temporal, parietal and occipital), the basal ganglia and the thalamus, and the brainstem and the cerebellar hemispheres on 1.5-tesla T2*-weighted gradient-recalled-echo MRI images. White matter lesions were semiquantified in fluid-attenuated inversion recovery images according to the Fazekas rating scale. Results: While the prevalence of MBs was comparable, MBs tended to be more abundant in DLB than in AD in all brain areas with the exception of the occipital lobes. The number of MBs was positively associated with the severity of white matter lesions but not with other vascular risk factors in either AD or DLB. The presence of MBs could be associated with cognitive impairment at onset. MB-positive DLB patients showed less impairment on ¹²³I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy) images, supporting the notion of an inverse relationship between vascular lesions and Lewy body pathology. Conclusion: It was suggested that an intricate association between Lewy body pathology, AD-type pathologies and vascular lesions seems to be related to the initial symptoms and results of MIBG scintigraphy in DLB.