Identification and Quantification of Jaundice by Trans-Conjunctiva Optical Imaging Using a Human Brain-like Algorithm: A Cross-Sectional Study.

Jaundice is caused by excess circulating bilirubin, known as hyperbilirubinemia. This symptom is sometimes caused by a critical hepatobiliary disorder, and is generally identified as yellowish sclera when bilirubin levels increase more than 3 mg/dL. It is difficult to identify jaundice accurately, especially via telemedicine. This study aimed to identify and quantify jaundice by trans-conjunctiva optical imaging. Patients with jaundice (total bilirubin ≥3 mg/dL) and normal control subjects (total bilirubin <3 mg/dL) were prospectively enrolled from June 2021 to July 2022. We took bilateral conjunctiva imaging with a built-in camera on a smartphone (1st generation iPhone SE) under normal white light conditions without any restrictions. We processed the images using an Algorithm Based on Human Brain (ABHB) (Zeta Bridge Corporation, Tokyo, Japan) and converted them into a hue degree of Hue Saturation Lightness (HSL) color space. A total of 26 patients with jaundice (9.57 ± 7.11 mg/dL) and 25 control subjects (0.77 ± 0.35 mg/dL) were enrolled in this study. The causes of jaundice among the 18 male and 8 female subjects (median age 61 yrs.) included hepatobiliary cancer (n = 10), chronic hepatitis or cirrhosis (n = 6), pancreatic cancer (n = 4), acute liver failure (n = 2), cholelithiasis or cholangitis (n = 2), acute pancreatitis (n = 1), and Gilbert's syndrome (n = 1). The maximum hue degree (MHD) optimal cutoff to identify jaundice was 40.8 (sensitivity 81% and specificity 80%), and the AUROC was 0.842. The MHD was moderately correlated to total serum bilirubin (TSB) levels (rS = 0.528, p < 0.001). TSB level (≥5 mg/dL) can be estimated by the formula 21.1603 - 0.7371 × 56.3-MHD2. In conclusion, the ABHB-based MHD of conjunctiva imaging identified jaundice using an ordinary smartphone without any specific attachments and deep learning. This novel technology could be a helpful diagnostic tool in telemedicine or self-medication.

The Characteristics and Prognosis of Alpha-Fetoprotein and Des-Gamma-Carboxy Prothrombin Double-Negative Hepatocellular Carcinoma at Baseline in Higher BCLC Stages.

Alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) are widely used as tumor markers to diagnose hepatocellular carcinoma (HCC). Some advanced HCCs demonstrate neither AFP nor DCP. This study investigated the characteristics and prognosis of AFP (<20 ng/mL) and DCP (<40 mAU/ml) double-negative HCC (DNHC) in higher-stage HCC. Between April 2012 and March 2022, 419 consecutive patients were enrolled with newly diagnosed HCC and 372 patients were selected that were diagnosed by histopathology and/or imaging. AFP-negative, DCP-negative, and double-negative HCC were identified in 262 patients (70.4%), 143 patients (38.2%), and 120 patients (32.3%), respectively. In higher-BCLC stages (BCLC-B, C, and D), 17 patients (14.7%) were DNHC. Although there was no difference in BCLC staging, there were more cases under TNM Stage III in DNHC (71.0% vs. 41.4%, p = 0.026). The median maximum tumor diameter was smaller in DNHC [3.2 (1.8−5.0) vs. 5.5 (3.5−9.0) cm, p = 0.001] and their median survival time was significantly better, even in higher-stage HCC [47.0 (24.0−84.0) vs. 19.0 (14.0−30.0) months, p = 0.027). DNHC in higher-BCLC stage HCC is independent of BCLC staging, characterized by a tumor diameter < 5 cm, and is treatable with a good prognosis.

[Small duct primary sclerosing cholangitis diagnosed after fever and liver disorder: a case report].

A woman in her 10s presented to our hospital with persistent fever and liver disorder and was admitted. It was considered that her fever was due to infectious, hematological, and collagen diseases; however, these diseases were excluded. Upper and lower gastrointestinal endoscopy revealed gastritis and indicated inflammatory bowel disease involvement. Neither bile duct stricture nor bile duct wall thickening was observed in the imaging. Thus, liver biopsy was performed due to worsening liver disorder. A diagnosis of small duct primary sclerosing cholangitis was made based on the findings of edematous enlargement of the portal tracts, neutrophilic infiltration, and destruction of the interlobular bile ducts. Furthermore, liver biopsy is helpful in diagnosing unknown liver disorders, even if no abnormality in the bile duct is observed on imaging.

Chronic Active Epstein-Barr Virus Infection Indistinguishable from Autoimmune Hepatitis: A Case Report.

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease, mainly affecting children, typically characterized by persistent infectious mononucleosis (IM)-like symptoms. We describe an adult case of CAEBV without IM-like symptoms, which was indistinguishable from autoimmune hepatitis (AIH). A 60-year-old woman with liver damage was diagnosed with AIH (International Diagnostic Score: 16 points). She had been treated with prednisolone for three years; however, her transaminases had never normalized. She was admitted for another liver biopsy due to repeated high fevers and worsening of her liver damage over two months. Her EBV-DNA copy number was 2.9 × 104 copies/µg DNA, and EBV-encoded small RNA1-positive lymphocytic infiltration was observed in both the present and previously collected (three years ago) liver tissue samples. This case implies that hepatic involvement in a CAEBV without IM-like symptoms is difficult to distinguish from AIH and may be misdiagnosed. In some steroid resistant AIH cases, evaluating for CAEBV may be valuable.

Steatosis is involved in the progression of kidney disease in a high-fat-diet-induced non-alcoholic steatohepatitis mouse model.

Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health issues associated with the metabolic syndrome. Although NASH is a known risk factor of CKD, the mechanisms linking these two diseases remain poorly understood. We aimed to investigate alterations in the kidney complicated with dyslipidemia in an established NASH mouse model. Male C57BL6/J mice were fed with control diet or high-fat diet (HFD), containing 40% fat, 22% fructose, and 2% cholesterol for 16 weeks. Metabolic characteristics, histological changes in the kidney, endoplasmic reticulum (ER) stress, apoptosis, and fibrosis were evaluated by histological analysis, immunoblotting, and quantitative reverse transcription-polymerase chain reaction. Levels of serum aspartate aminotransferase, alanine aminotransferase, alkali-phosphatase, total cholesterol, and urinary albumin were significantly higher in mice fed with HFD. Remarkable steatosis, glomerular hypertrophy, and interstitial fibrosis were also shown in in the kidney by leveraging HFD. Furthermore, HFD increased the mRNA expression levels of Casp3, Tgfb1, and Nfe2l2 and the protein level of BiP. We observed the early changes of CKD and speculate that the underlying mechanisms that link CKD and NASH are the induction of ER stress and apoptosis. Further, we observed the activation of Nfe2l2 in the steatosis-induced CKD mouse model. This NASH model holds implications in investigating the mechanisms linking dyslipidemia and CKD.

Pemafibrate Ameliorates Liver Dysfunction and Fatty Liver in Patients with Non-Alcoholic Fatty Liver Disease with Hypertriglyceridemia: A Retrospective Study with the Outcome after a Mid-Term Follow-Up.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome. No standard pharmacological treatment has yet been established. We retrospectively evaluated the efficacy of pemafibrate in 16 NAFLD patients (11 men and 5 women; median age, 59 years; range, 27-81 years) who had taken pemafibrate for at least one year. They were all diagnosed with fatty liver according to imaging and clinical criteria. They were administered pemafibrate from October 2018 to October 2021 (median, 94 weeks; range, 56-157 weeks). Serum triglyceride was significantly decreased by -41.9% (342.3 ± 54.0 to 198.9 ± 20.4 mg/dL, p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase, and gamma-glutamyl transferase levels significantly decreased by -42.1% (49.6 ± 7.0 to 28.7 ± 3.4 U/L, p < 0.001), -57.1% (65.1 ± 10.8 to 27.9 ± 3.7 U/L, p < 0.001), and -43.2% (68.9 ± 10.9 to 39.1 ± 5.3 U/L, p < 0.05), respectively. The AST to platelet ratio (APRI) (0.8 ± 0.1 to 0.4 ± 0.1, p < 0.001) and fibrosis based on four factors (FIB-4) index (1.8 ± 0.3 to 1.4 ± 0.2, p < 0.05) also significantly decreased. Liver attenuation (39.1 ± 1.2 to 57.8 ± 2.7 HU, p = 0.028) and liver/spleen ratio (0.76 ± 0.04 to 1.18 ± 0.02, p = 0.012) significantly improved in three patients, as assessed by computed tomography. In conclusion, pemafibrate significantly improves serum triglyceride levels, liver function, FIB-4 index, APRI, and fatty liver in NAFLD patients with hypertriglyceridemia.

A vein-viewing application enabled detecting abdominal wall varices related to the presence of non-treated gastroesophageal varices: a cross-sectional study.

BACKGROUND: Gastroesophageal varices (GOV) are a life-threatening complication in chronic liver disease. A method for non-invasively predicting GOV is crucial for management. This study aimed to determine whether a vein-viewing application can detect abdominal wall varices (AWV) and elucidate the relationship between AWV and GOV. METHODS: One-hundred patients with chronic liver diseases were prospectively enrolled. All the patients underwent esophagogastroduodenoscopy within three months of the enrollment. Unmanipulated images (UI) and vein-weighted images (VWI) were taken for assessing AWV by a vein-viewing application on iPhone. Two doctors independently evaluated both image types. We defined the grading of both UI and AWV as grade 0 (non-detectable), grade 1 (slightly detectable), and grade 2 (distinct). RESULTS: The causes of liver diseases among the 71 men and 29 women (median age, 70.5 yr) included Hepatitis B (n = 19), Hepatitis C (n = 21), alcoholism (n = 33), primary biliary cholangitis (n = 3), autoimmune hepatitis (n = 4) and others (n = 20). GOV was indicated in 60 patients, and half of them had not been treated previously (non-treated). VWI could significantly visualize AWV than UI (72% vs. 24%, p = 0.0005). The presence of cirrhosis (chronic hepatitis vs. cirrhosis = 64.6% vs. 91.4%, p = 0.004) and GOV (52.3% vs. 74.3%, p = 0.032) were significantly higher in the VWI-AWV grade 2 group. Multivariate analysis demonstrated that VWI-AWV grade 2 was an independent factor related to the presence of non-treated GOV [OR = 3.05 (1.24-7.53), p = 0.016]. CONCLUSIONS: The vein-viewing application non-invasively detected AWV related to the presence of cirrhosis and GOV, and VWI-AWV grade 2 was an independent factor related to the presence of non-treated GOV.

Newly Invented Micellized Vitamin K2 Recovered Prolonged Prothrombin Time under Obstructive Jaundice in Rats with Bile Duct Ligation.

In cholestatic liver diseases, coagulopathy is induced by malabsorption of vitamin K. Supplementation of vitamin K has previously been shown to prevent coagulopathy. In this study, we tested the efficacy of a newly invented micellized vitamin K2 (m-vitK2) in treating coagulopathy, using a rat bile duct ligation (BDL) model. Experiment 1: m-vitK2 (0.3 mg/kg) or m-vitK2 (0.3 mg/kg) mixed with taurocholic acid (TA) (10 mg/body) was orally administrated every day for 7 d from the fourth day after BDL (n=6 for each). Experiment 2: To evaluate absorption, m-vitK2 (0.3 mg/kg) with or without TA (10 mg/body) was orally administered on the fourth day after BDL and compared with the untreated control BDL (n=2 for each). These data were compared with sham-operated (n=6) and untreated control BDL rats (n=6). The m-vitK2 recovered prothrombin time (PT) in Experiment 1 (control 42.7±5.7 s vs. m-vitK2 24.0±9.3 s, p<0.05). Experiment 2 demonstrated that the mixture of m-vitK2 and TA enhanced absorption compared to m-vitK2 alone. Moreover, in Experiment 1, m-vitK2 mixed with TA completely recovered PT (control 42.7±5.7 s vs. m-vitK2+TA 14.9±1.2 s, p<0.01). Micelle sizes decreased with the m-vitK2 and TA treatment (m-vitK2 86.3±5.6 nm vs. m-vitK2+TA 71.9±4.7 nm, p<0.05). Orally administered, newly invented m-vitK2 recovered coagulopathy even under obstructive jaundice. TA decreased the mean micelle size and improved m-vitK2 absorption.

Erratum for Ikeda et al., "Pemafibrate Dramatically Ameliorated the Values of Liver Function Tests and Fibrosis Marker in Patients with Non-Alcoholic Fatty Liver Disease".

[This corrects the article DOI: 10.33160/yam.2020.08.009.].

Pemafibrate Dramatically Ameliorated the Values of Liver Function Tests and Fibrosis Marker in Patients with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome, which can progress to liver cirrhosis. Standard medication has not been established. Pemafibrate is a selective peroxisome proliferator-activated receptor (PPAR) α modulator. We retrospectively evaluated the efficacy of pemafibrate in patients with NAFLD. METHODS: We retrospectively enrolled 17 patients (ten men, seven women; median age, 63 years; range, 27-81 years). They were all proven to have fatty liver through imaging and had little or no history of drinking (ethanol consumption of < 20 g/day for women and < 30 g/day for men). They were administered pemafibrate from October 2018 to June 2020. RESULTS: After administration, serum triglyceride (TG) tended to be decreased (300.5 ± 22.5 to 239.5 ± 34.3 mg/dL, P = 0.06). Serum high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol levels did not change. ALT was significantly decreased (-47.4%) for six months (57.5 ± 8.8 to 30.3 ± 5.8 U/L, P < 0.01). The values of serum GGT significantly decreased (-48.7%) for sixth months (63.9 ± 10.3 to 32.8 ± 6.6 U/L, P < 0.01). Aspartate aminotransferase (AST) to platelet ratio (APRI), a fibrosis marker, also was significantly decreased in the sixth month (0.7 ± 0.1 to 0.4 ± 0.1, P < 0.05). Body mass index (BMI) and hemoglobin A1c (HbA1c) showed no significant change. CONCLUSION: Pemafibrate dramatically ameliorated the values of liver function tests and APRI in patients with NAFLD.

Metal hydride-based materials towards high performance negative electrodes for all-solid-state lithium-ion batteries.

Electrode performances of MgH2-LiBH4 composite materials for lithium-ion batteries have been studied using LiBH4 as the solid-state electrolyte, which shows a high reversible capacity of 1650 mA h g(-1) with an extremely low polarization of 0.05 V, durable cyclability and robust rate capability.

Anode properties of magnesium hydride catalyzed with niobium oxide for an all solid-state lithium-ion battery.

The anode properties of pristine MgH2 and MgH2 catalyzed with Nb2O5 have been investigated for an all solid-state lithium-ion battery. The catalytic effect stabilizes the plateau voltage as a result of kinetic improvement of the hydrogen transfer from the Mg phase to the Li phase.

Intracellular responses of antennal chordotonal sensilla of the American cockroach.

The responses of mechanoreceptor neurons in the antennal chordotonal organ have been examined in cockroaches by intracellular recording methods. The chordotonal organ was mechanically stimulated by sinusoidal movement of the flagellum. Stimulus frequencies were varied between 0.5 and 150 Hz. Receptor neurons responded with spike discharges to mechanical stimulation, and were classed into two groups from plots of their average spike frequencies against stimulus frequency. Neurons in one group responded to stimulation over a wide frequency range (from 0.5 to 150 Hz), whereas those in a second group were tuned to higher frequency stimuli. The peak stimulus frequency at which receptor neurons showed maximum responses differed from cell to cell. Some had a peak response at a stimulus frequency given in the present study (from 0.5 to 150 Hz), whereas others were assumed to have peak responses beyond the highest stimulus frequency examined. The timing for the initiation of spikes or of a burst of spikes plotted against each stimulus cycle revealed that spike generation was phase-locked in most cells. Some cells showed phase-independent discharges to stimulation at lower frequency, but increasing stimulus frequencies spike initiation began to assemble at a given phase of the stimulus cycle. The response patterns observed are discussed in relation to the primary process of mechanoreception of the chordotonal organ.