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Abstract Background: Vascular endothelial growth factor (VEGF) exerts its actions on the microvasculature, by interacting with specific endothelial cell receptors, and thus, contributes to angiogenesis and growth in many tumours. Methods: Using nested reverse-transcription–polymerase chain reaction, we examined the biopsy specimens of 14 patients with human hepatocellular carcinoma (HCC) and cirrhosis, for the expression of hepatic VEGF, and the VEGF receptors KDR and flt-1. To avoid the influence of hypoxia or ischaemia induced by surgical manipulation, we used biopsy specimens of the liver instead of resected specimens. Results: Vascular endothelial growth factor mRNA expression was detected in the tumour portion of the specimens in 13 of 14 patients (93%), and in the corresponding non-tumour portion of the specimens in eight patients (57%; P = 0.08). No differences were found between the tumour portion and the corresponding non-tumour portion in relative concentrations of VEGF mRNA. However, mRNA expression of the VEGF receptors, KDR and flt-1, was detected in 14 (100%) and 11 (79%) of the tumour portions, respectively, and in four (29%) and five (36%) of the corresponding non-tumour portions, respectively (χ test: KDR, P < 0.01; flt-1, P = 0.08). The relative concentration of KDR mRNA in the tumour portions was significantly higher than in the non-tumour portions (Mann–Whitney U-test: P < 0.001) but no differences were detected for flt-1. Conclusions: KDR mRNA is significantly overexpressed in HCC lesions and could be associated with the angiogenesis and tumour growth induced by VEGF. [ABSTRACT FROM AUTHOR]

Background and Aim: SmartExam is a novel computational method compatible with FibroScan that uses a software called SmartDepth and continuous controlled attenuation parameter measurements to evaluate liver fibrosis and steatosis. This retrospective study compared the diagnostic accuracy of conventional and SmartExam‐equipped FibroScan for liver stiffness measurement (LSM). Methods: The liver stiffness and the associated controlled attenuation parameters of 167 patients were measured using conventional and SmartExam‐Equipped FibroScan as well as reference methods like magnetic resonance elastography (MRE) and magnetic resonance imaging‐based proton density fat fraction (MRI‐PDFF) measurements to assess its diagnostic performance. M or XL probes were selected based on the probe‐to‐liver capsule distance for all FibroScan examinations. Results: The liver stiffness and controlled attenuation parameter (CAP) correlation coefficients calculated from conventional and SmartExam‐equipped FibroScan were 0.97 and 0.82, respectively. Using MRE/MRI‐PDFF as a reference and the DeLong test for analysis, LSM and the area under the receiver operating characteristic curve for CAP measured by conventional and SmartExam‐equipped FibroScan showed no significant difference. However, the SmartExam‐equipped FibroScan measurement (33.6 s) took 1.4 times longer than conventional FibroScan (23.2 s). Conclusions: SmartExam has a high diagnostic performance comparable with that of conventional FibroScan. Because the results of the conventional and SmartExam‐equipped FibroScan were strongly correlated, it can be considered useful for assessing the fibrosis stage and steatosis grade of the liver in clinical practice, with less variability but little longer measurement time compared with the conventional FibroScan. [ABSTRACT FROM AUTHOR]

Background and Aim: In the condition of high prevalence of non‐alcoholic fatty liver disease (NAFLD), a new diagnostic algorithm to efficiently identify NAFLD patients with significant fibrosis is urgently required. We evaluated the predictive ability of the fibrosis‐4 index (FIB‐4 index) for significant liver fibrosis (F ≥ 2) in a cohort of Japanese patients with NAFLD. Methods: We prospectively calculated the FIB‐4 index in patients who were incidentally diagnosed as fatty liver in medical checkups and then conducted liver stiffness measurement by vibration‐controlled transient elastography (VCTE) only in patients in whom the FIB‐4 index was more than the low cut‐off index (> 1.45). Results: Of the 5929 people who underwent medical checkups, a total of 1374 people were identified as having fatty liver. Among these, we performed VCTE in 106 patients in whom the FIB‐4 index was higher than 1.45. The distribution of the fibrosis stage as estimated by VCTE in the patients was as follows: F0, 52.8%; F1, 10.3%; F2, 21.6%; F3, 11.3%; and F4, 3.7%. The positive predictive value of the FIB‐4 index for detecting NAFLD with significant fibrosis was 36.6%. The minimum value of the FIB‐4 index was constant for each estimated fibrosis stage. Conclusions: This is the first prospective study to evaluate the usefulness of the FIB‐4 index as the first step to screen NAFLD patients with significant fibrosis. In Japan, addition of one further step that combined with the FIB‐4 index is necessary to meaningfully reduce the number of patients needing liver stiffness measurement or liver biopsy. [ABSTRACT FROM AUTHOR]

Background and Aims: The Baveno VI criteria enable non‐invasive screening for esophageal varices. However, these criteria were established based on studies examining a large proportion of patients with viral hepatitis and relatively few patients with non‐alcoholic fatty liver disease (NAFLD). Furthermore, because vibration‐controlled transient elastography (VCTE) has a high incidence of measurement error, improved criteria are needed. We aimed to develop criteria based on magnetic resonance elastography (MRE) even among patients with NAFLD. Methods: We performed a cross‐sectional analysis of patients who had undergone MRE and/or VCTE as well as an esophagogastroduodenoscopy. The patients were classified as having either a low risk or a high risk of varices. The optimal cut‐offs for ruling out esophageal varices were calculated for the MRE and VCTE liver stiffness measurement (LSM), the platelet count in an estimation cohort, and the cut‐offs were then evaluated using validation cohorts composed of patients who had undergone only MRE or VCTE. Results: The study included 627 patients (39% with NAFLD). The optimal cut‐off values for the MRE‐LSM and the platelet count were 4.2 kPa and 18.0 × 104/μL, respectively. An MRE‐LSM of 4.2 kPa plus a platelet count of 18.0 × 104/μL had a negative predictive value of 1.00 for both low‐risk plus high‐risk varices as well as for high‐risk varices in a validation cohort, enabling the presence of varices to be ruled out. Conclusions: Magnetic resonance elastography might enable a safer avoidance of screening endoscopy, with a smaller measurement error, among patient populations with a high prevalence of NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aim: The aim of this study was to assess the efficacy of a new microwave ablation (MWA) system, the Emprint Ablation System, for the ablation of unresectable large liver tumors (≥ 30 mm). Methods: Twenty‐one hepatic tumors (mean diameter, 34.7 mm) from 21 patients who underwent percutaneous MWA were included in this cross‐sectional study. A volume analyzer based on computed tomography imaging was used for all patients within the month before and month after the procedure to evaluate the shape and volume of ablation zones. In addition, computed tomography imaging was performed again 3 months after the procedure to evaluate the presence of residual tumors and local recurrence. Results: Mean ablation time was 11.3 min, and mean overall procedure time was 33.4 min. An ablated adrenal gland‐induced Takotsubo (stress) cardiomyopathy occurred immediately after MWA as a major complication in one patient. Roundness index A, B, and C presented a mean value of 0.94, 0.94, and 1.01, respectively (all values near 1 is a perfect sphere), indicating that a spherical ablation zone was achieved. The mean ablation volume was larger than the volume of tumors (24.5 vs 41.7 cm3). Residual tumors were confirmed in only 4.8% of tumors after a single ablation session. There was no local recurrence. Conclusions: In our experience, the new MWA system provides an effective treatment option for unresectable large liver tumors. However, to ablate the liver tumors safely, it is necessary to consider the surrounding organs, such as the adrenal glands. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: The fibrosis stage of liver is associated with the long‐term outcomes in patients with non‐alcoholic fatty liver disease (NAFLD). However, significant fibrosis, defined as fibrosis stages 2–4, is associated with an elevated risk of progression to severe liver disease; there have been scant reports about diagnosing significant fibrosis. We compare the noninvasive method and aim to identify appropriate liver fibrosis markers for detecting significant fibrosis in NAFLD patients. Methods: We compared the usefulness of liver fibrosis markers (Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein [WFA+‐M2BP], type 4 collagen 7S, etc.), clinical scoring systems, and liver stiffness measurement obtained using vibration‐controlled transient elastography and magnetic resonance imaging‐based magnetic resonance elastography in the same individuals and identified the most appropriate noninvasive method for detecting significant fibrosis in 165 patients with liver biopsy‐diagnosed NAFLD. Results: The area under the receiver operating characteristic curve based on the serum cutoff index values of WFA+‐M2BP/the serum levels of type IV collagen 7S for the diagnosis of significant fibrosis was 0.832 (95% confidence interval: 0.771–0.894)/0.837 (95% confidence interval: 0.778–0.898). “WFA+‐M2BP (cutoff index) ≥ 0.83 or type IV collagen 7S ≥ 5.2 ng/mL” showed a high sensitivity (91.4%) and negative predictive value (87.9%) for the diagnosis of significant fibrosis. Conclusions: We showed that serum WFA+‐M2BP or type IV collagen 7S levels serve as useful independent markers for detecting significant fibrosis and that use of both WFA+‐M2BP and type IV collagen 7S together increased the sensitivity and negative predictive value for the diagnosis of liver fibrosis. These results need to be validated in larger populations from multiple clinical centers. [ABSTRACT FROM AUTHOR]

Background and Aim Major depressive disorder ( MDD) is an important public health problem, and it is often comorbid with many chronic diseases. The purpose of this study was to identify the clinical features of non-alcoholic fatty liver disease ( NAFLD) patients comorbid with MDD and to investigate the influence of MDD on the effect of treatment in patients with NAFLD. Methods A total of 258 patients with biopsy-proven NAFLD were included. MDD was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. The patients were followed up for 48 weeks under standard care for NAFLD, which consisted mainly of lifestyle modification. Results There were 32 patients comorbid with MDD. They were characterized by more severe histological steatosis and higher NAFLD activity score, and also significantly higher levels of serum aminotransferase, γ-glutamyl transpeptidase and ferritin, than age-and-sex-matched NAFLD patients without MDD. Moreover, NAFLD patients with MDD showed poor response to the standard care for NAFLD, in body weight loss and in other parameters. Particularly, NAFLD patients with unstable MDD (not in full/partial remission) showed severe resistance to the treatment. Conclusion This is the first study to demonstrate the clinical features and response to therapy of NAFLD patients comorbid with MDD. The comorbid state of MDD was associated with more severe histological liver steatosis and worse treatment outcomes in patients with NAFLD. Further investigations are required to develop new lifestyle modification programs that enable NAFLD patients with MDD to achieve the treatment goal. [ABSTRACT FROM AUTHOR]