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The article presents a case study of a 72-year-old woman with Child-Pugh B cirrhosis who was hospitalized for transarterial chemoebolization (TACE) for the recurrence of hepatocellular carcinoma with biliary invasion.

The article assesses the safety and long-term efficacy of ultrasonographically guided percutaneous radiofrequency ablation for tumours in the hepatic dome with intrapleural infusion. The researchers performed intrapleural fluid infusion in 587 patients for tumours in the hepatic dome. Based on the results, the study showed that radiofrequency ablation for tumours in the dome was safe and effective due to intrapleural fluid infusion.

Summary: Perihepatic lymph node enlargement (PLNE) which has been shown to be negatively associated with hepatocellular carcinoma (HCC) occurrence is frequently observed in chronic liver disease; however, changes in the state of perihepatic lymph nodes after eradication of hepatitis C virus (HCV) have not been investigated yet. We aimed to evaluate this issue. We enrolled 472 patients with chronic HCV infection who achieved viral eradication with direct‐acting antivirals (DAA). We investigated whether the status of perihepatic lymph nodes changed before and after HCV eradication (primary endpoint). We also evaluated the association between PLNE and clinical findings such as liver fibrosis or hepatocellular injury before HCV eradication (secondary endpoint). Perihepatic lymph node enlargement was detected in 164 of 472 (34.7%) patients before DAA treatment. Surprisingly, disappearance of PLNE was observed in 23.8% (39 patients) of all PLNE‐positive patients after eradication of HCV. Disappearance of PLNE was not associated with baseline clinical parameters or changing rates of clinical findings before and after DAA treatment. At baseline, presence of PLNE was significantly associated with a lower serum HCV‐RNA level (P = .03), a higher serum AST level (P = .004) and a higher ALT level (P < .001) after adjustment for sex and age. In conclusion, PLNEs became undetectable after DAA treatment in 23.8% of PLNE‐positive patients. Further study with a longer follow‐up period is needed to clarify the clinical importance of this phenomenon especially in relationship with the risk of HCC development. [ABSTRACT FROM AUTHOR]

This study integrates time-variable Gravity Recovery and Climate Experiment (GRACE) gravimetric measurements and Global Land Data Assimilation System (GLDAS) land surface models (LSM) in order to understand the inter-annual variations and groundwater storage changes (GWSC) in the Nzoia River Basin in Kenya, using the water balance equation and parameters. From averaged GRACE and GWSC data, the results showed that over the 10-year period, the basin experienced a groundwater depth gain of 6.38 mm year−1, which is equivalent to aquifer recharge of 298 million cubic metres (mcm) year−1. The deseasonalized groundwater variation analysis gave a net gain in groundwater storage of 6.21 mm year−1that is equal to a groundwater recharge gain of 290 mcm year−1. The observed results are comparable to the groundwater safe yield of 330 mcm year−1as estimated by the Water Resource Management Authority in Kenya. Through cross-plotting and analysis with averaged satellite altimetry data andin situmeasurements from rainfall and streamflow discharge, the total water storage change (TWSC) and GWSC in the basin were consistent and closely correlated in variation trends. The inter-annual standard deviation of groundwater change was determined as ±0.24 mm year−1, which is equivalent to 85% degree of confidence in the obtained results. The results in this study show that GRACE gravity-variable solutions and GLDAS-LSM provide reliable data sets suitable for the study of small to large basin groundwater storage variations, especially in areas with scarce and sparsely availablein situdata. [ABSTRACT FROM PUBLISHER]

Background: Percutaneous radiofrequency ablation (RFA) of liver tumours adjacent to the gastrointestinal tract is controversial. This study assessed the value of an intraperitoneal water infusion (artificial ascites) technique for percutaneous RFA of such tumours. Methods: Before ablation in 52 patients (55 treatments, 58 tumours), between 250 and 3000 (mean 681) ml 5 per cent glucose solution was infused into the abdominal cavity using a 14-G needle, with the aim of preventing thermal injury by separating the liver from the gastrointestinal tract. Results: There were no adverse events associated with the artificial ascites technique. In 43 (78 per cent) of the 55 treatments, the liver and gastrointestinal tract were separated successfully. In the other 12 treatments, in which the separation was not confirmed by real-time ultrasonography, there was one case of perforation of the ascending colon after RFA; adhesion of the liver and colon resulting from previous laparotomy may have been related to the injury. Conclusion: Production of artificial ascites can be undertaken safely, making RFA safe and effective for hepatic tumours adjacent to the gastrointestinal tract. In patients with possible postoperative adhesions, confirmation of separation of the liver from surrounding organs is mandatory to avoid thermal injury. [ABSTRACT FROM AUTHOR]

Background and aims: Percutaneous tumour ablation (PTA), such as ethanol injection and radiofrequency ablation, is now recognised as a primary treatment for hepatocellular carcinoma (HCC). Although PTA is a relatively safe procedure, it can cause biliary obstruction as a rare complication. As patients with cirrhosis undergoing surgery or endoscopic retrograde cholangiopancreatography/sphincterotomy have a high mortality rote from bleeding, we adopted the use of endoscopic papillary balloon dilatation (EPBD) in these patients and now report the results. We retrospectively analysed the incidence of biliary obstruction after PTA and the efficacy of treatment with EPBD. Patients and methods: A total of 1043 patients with HCC were treated by PTA, of whom 538 were treated with transarterial embolisation with up to eight years of follow up. Results: There were 17(1.6%) cases of hilar obstruction due to tumour progression and 35 (3.4%) cases of extrahepatic obstruction. Apart from the expected causes of biliary obstruction (haemobilia n = 11, gallstones n = 11, and three miscellaneous causes), we found that 10 patients had obstruction due to biliary casts. This is the first description of biliary casts after percutaneous tumour ablation therapy. Extrahepatic biliory obstruction by procedure related haemobilia occurred within three days of PTA while other causes occurred between 0 and 17 (average 4.9) months. Biliary casts occurred more frequently after ethanol injection than after radiofrequency ablation. EPBD successfully dissipated biliary obstruction in 33 of 35 cases, while two died due to hepatic failure despite successful drainage. Conclusions: Extrahepatic biliary obstruction is an uncommon complication after PTA for HCC, and can be safely and effectively treated with EPBD, despite impaired liver function. [ABSTRACT FROM AUTHOR]

Aim: The incidence of and factors involved in gastroesophageal varix-related events in hepatitis C virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear., Methods: We conducted a multicenter study using prospective data from 478 hepatitis C virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria. Patients without varix or with F1 without red color signs were defined as low-risk varix, and patients with ≥F2 or red color signs or a history of rupture were defined as high-risk varix. Varix-related events were defined as prophylactic treatment or rupture of gastroesophageal varix., Results: The median age was 70 years, 43% of patients had decompensated cirrhosis, and 16% had high-risk varices (13% in compensated and 33% in decompensated, p < 0.001). Sustained virologic response rates were 94.9% for compensated cirrhosis and 91.3% for decompensated cirrhosis (p = 0.120). Across 35.7 months, 25 patients received prophylactic treatment, and four experienced varix rupture. The 3-year incidence rate of varix-related events was 6.2% (3.5% in compensated and 9.9% in decompensated, p = 0.001). In the multivariate analysis, high-risk varix (p < 0.001), high baseline gamma-glutamyl transpeptidase levels (p < 0.001), and virologic failure (p = 0.004) were significantly involved in varix-related events., Conclusions: The cumulative incidence rate of varix-related events was significantly higher in decompensated cirrhosis than in compensated cirrhosis. Baseline varix status, baseline gamma-glutamyl transpeptidase levels, and virologic response were related to varix-related events after direct-acting antiviral therapy., (© 2024 The Author(s). Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Background: Implantable cardioverter defibrillators (ICDs) reduce mortality associated with ventricular arrhythmia in high-risk patients with cardiovascular disease. Machine learning (ML) approaches are promising tools in arrhythmia research; however, their application in predicting ventricular arrhythmias in patients with ICDs remains unexplored. We aimed to predict and stratify ventricular arrhythmias requiring ICD therapy using 12-lead electrocardiograms (ECGs) in patients with an ICD., Methods and Results: This retrospective analysis included 200 adult patients who underwent ICD implantation at a single center. Patient demographics, clinical features, and 12-lead ECG data were collected. Unsupervised learning techniques, including K-means and hierarchical clustering, were used to stratify patients based on 12-lead ECG features. Dimensionality reduction methods were also used to optimize clustering accuracy. The silhouette coefficient was used to determine the optimal method and number of clusters. Of the 200 patients, 59 (29.5%) received appropriate therapy. The mean age of patients was 62.3 years, and 81.0% were male. The mean follow-up period was 2,953 days, with no significant intergroup differences. Hierarchical clustering into 3 clusters proved to be the most accurate (silhouette coefficient=0.585). Kaplan-Meier curves for these 3 clusters revealed significant differences (P=0.026)., Conclusions: We highlight the potential of ML-based clustering using 12-lead ECGs to help in the risk stratification of ventricular arrhythmia. Future research in a larger multicenter setting may provide further insights and refine ICD indications.

Competing Interests: Declaration of Competing Interest Yousuke Nakai has received research grants by Taiho Pharmaceutical. No funding agency had input into the design and conduct of this study.

Aim: A nationwide survey in 2018 showed decreasing involvement of viral hepatitis and increasing involvement of nonviral liver diseases in the etiology of liver cirrhosis (LC) in Japan. An updated nationwide survey was undertaken in 2023., Methods: Cases of LC diagnosed between 2018 and 2021 were collected from 75 institutions, and the etiologies of LC were investigated. In addition, the data obtained were compared with the results of previous studies., Results: Among the 15 517 cases, alcohol-related liver disease (ALD)-associated LC was the most frequent cause (n = 5,487, 35.4%). Hepatitis C virus-associated LC, nonalcoholic steatohepatitis (NASH)-associated LC, and hepatitis B virus-associated LC were ranked as second, third, and fourth, respectively. In comparison to the previous survey, the ratios of viral hepatitis-associated LC decreased (HBV: from 11.5% to 8.1%; HCV: from 48.2% to 23.4%), while the ratios of ALD-associated LC and NASH-associated LC increased (from 19.9% to 35.4% and from 6.3% to 14.6%, respectively). Regarding cases of LC with hepatocellular carcinoma (n = 5906), HCV-associated LC (1986 cases, 33.6%) was the most frequent cause. Alcohol-related liver disease-associated LC, NASH-associated LC, and HBV-associated LC were the second-, third-, and fourth-ranked causes, respectively. In comparison to the previous survey, as the cause of hepatocellular carcinoma-complicated LC, HCV-associated LC decreased from 60.3% to 33.6%, while the ratios of ALD-associated LC and NASH-associated LC increased from 14.2% to 28.6% and from 4.2% to 14.0%, respectively., Conclusions: The major causes of LC in Japan are suggested to have been shifting from viral hepatitis to nonviral chronic liver diseases., (© 2024 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Chronic hepatitis B and C are among the most significant infectious diseases worldwide, and are major risk factors for liver cirrhosis and liver cancer. In Japan, comprehensive hepatitis measures are implemented for the testing and treatment of viral hepatitis, thus enabling the early diagnosis of liver cancer. Nevertheless, patients with decompensated cirrhosis and liver cancer often have unfavorable prognoses and require repetitive long-term treatment. In fiscal year 2018, an integrated policy of medical expense subsidies and research was established in Japan that aimed to alleviate patients' financial burden and launch the clinical registry of advanced liver disease. Over time, updates to the eligibility for the subsidy increased access to patients and has led to an increased number of beneficiaries. Additionally, the accumulation of clinical data in the registry has revealed the treatment choices for these diseases. However, the disparities in efforts across prefectures have also become evident. Raising public awareness of the policy and tightening the multisector healthcare network are keys to success in supporting qualifying patients with advanced liver disease., (© 2024 Japan Society of Hepatology.)

The proto-oncogene MYCN expression marked a cancer stem-like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118). Serum MYCN protein levels were assessed in healthy controls (N = 15), patients with HCC (N = 116), pre- and post-surgical patients with HCC (N = 20), and a subset of patients from a phase 3 clinical trial of ACR (N = 68, NCT01640808). The results showed increased MYCN gene expression in HCC tumors, which positively correlated with HCC recurrence in non-cirrhotic or single-tumor patients. Serum MYCN protein levels were higher in patients with HCC, decreased after surgical resection of HCC, and were associated with liver functional reserve and fibrosis markers, as well as long-term HCC prognosis (>4 years). Subgroup analysis of a phase 3 clinical trial of ACR identified serum MYCN as the risk factor most strongly associated with HCC recurrence. Patients with HCC with higher serum MYCN levels after a 4-week treatment of ACR exhibited a significantly higher risk of recurrence (hazard ratio 3.27; p = .022). In conclusion, serum MYCN holds promise for biomarker-based precision medicine for the prevention of HCC, long-term prognosis of early-stage HCC, and identification of high-response subgroups for ACR-based treatment., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: We investigated the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) and attenuation imaging (ATI) in detecting fibrosis and steatosis in patients with chronic liver disease (CLD), comparing them with established methods., Methods: In 190 patients with CLD, 2D-SWE and vibration-controlled transient elastography (VCTE) were used for liver stiffness measurement (LSM), and ATI and controlled attenuation parameter (CAP) were used for steatosis quantification. The correlations between these new and established methods were analyzed., Results: Significant correlations were found between 2D-SWE and VCTE (r = 0.78, P < 0.001), and between ATI and CAP (r = 0.70, P < 0.001). Liver stiffness tended to be lower with 2D-SWE compared with that with VCTE, especially in cases with higher LSM, and ATI was less influenced by skin-capsular distance than CAP. Area under the receiver-operating characteristics curves (AUCs) and optimal cut-offs of 2D-SWE for diagnosing liver fibrosis stages F2, F3, and F4 were 0.73 (8.7 kPa), 0.79 (9.1 kPa), and 0.88 (11.6 kPa), respectively. The AUCs and optimal cut-offs of ATI for diagnosing hepatic steatosis grades S1, S2, and S3 were 0.91 (0.66 dB/cm/MHz), 0.80 (0.79 dB/cm/MHz), and 0.88 (0.86 dB/cm/MHz), respectively. A subgroup analysis of 86 patients with metabolic dysfunction-associated steatotic liver disease also demonstrated good performance for 2D-SWE and ATI., Conclusion: 2D-SWE and ATI performed comparably with conventional VCTE and CAP in evaluating CLD, offering reliable alternatives for diagnosing liver fibrosis and steatosis., (© 2024. The Author(s).)

Exposure to N 2 O 5 generated by plasma technology activates immunity in Arabidopsis through tryptophan metabolites. However, little is known about the effects of N 2 O 5 exposure on other plant species. Sweet basil synthesizes many valuable secondary metabolites in its leaves. Therefore, metabolomic analyses were performed at three different exposure levels [9.7 (Ex1), 19.4 (Ex2) and 29.1 (Ex3) μmol] to assess the effects of N 2 O 5 on basil leaves. As a result, cinnamaldehyde and phenolic acids increased with increasing doses. Certain flavonoids, columbianetin, and caryophyllene oxide increased with lower Ex1 exposure, cineole and methyl eugenol increased with moderate Ex2 exposure and L-glutathione GSH also increased with higher Ex3 exposure. Furthermore, gene expression analysis by quantitative RT-PCR showed that certain genes involved in the syntheses of secondary metabolites and jasmonic acid were significantly up-regulated early after N 2 O 5 exposure. These results suggest that N 2 O 5 exposure increases several valuable secondary metabolites in sweet basil leaves via plant defense responses in a controllable system., (© 2024. The Author(s).)

Background and Aims: Identifying patients with steatotic liver disease who are at a high risk of developing HCC remains challenging. We present a deep learning (DL) model to predict HCC development using hematoxylin and eosin-stained whole-slide images of biopsy-proven steatotic liver disease., Approach and Results: We included 639 patients who did not develop HCC for ≥7 years after biopsy (non-HCC class) and 46 patients who developed HCC <7 years after biopsy (HCC class). Paired cases of the HCC and non-HCC classes matched by biopsy date and institution were used for training, and the remaining nonpaired cases were used for validation. The DL model was trained using deep convolutional neural networks with 28,000 image tiles cropped from whole-slide images of the paired cases, with an accuracy of 81.0% and an AUC of 0.80 for predicting HCC development. Validation using the nonpaired cases also demonstrated a good accuracy of 82.3% and an AUC of 0.84. These results were comparable to the predictive ability of logistic regression model using fibrosis stage. Notably, the DL model also detected the cases of HCC development in patients with mild fibrosis. The saliency maps generated by the DL model highlighted various pathological features associated with HCC development, including nuclear atypia, hepatocytes with a high nuclear-cytoplasmic ratio, immune cell infiltration, fibrosis, and a lack of large fat droplets., Conclusions: The ability of the DL model to capture subtle pathological features beyond fibrosis suggests its potential for identifying early signs of hepatocarcinogenesis in patients with steatotic liver disease., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: A simple noninvasive score, the Agile 3+ score, combining liver stiffness measurement, aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for the identification of advanced fibrosis in patients with suspected NAFLD. We performed a systematic review and meta-analysis of observational studies to evaluate the diagnostic accuracy of the Agile 3+ score in identifying patients with NAFLD and advanced fibrosis. Recently, an International consensus changed the nomenclature of NAFLD into metabolic-associated steatotic liver disease, so currently, the two terms are interchangeable., Approach and Results: We systematically searched MEDLINE, Ovid Embase, Scopus, and Cochrane Library electronic databases for full-text published articles in any language from the inception to the April 24, 2023. We included original articles reporting data on the sensitivity and specificity of the Agile 3+ score, according to previously described rule-out (≤ 0.451) and rule-in (≥ 0.679) cutoffs. We included 6 observational studies (total of 6955 participants) with biopsy-proven NAFLD [mean age 53 (SE 4) years, mean body mass index 30.9 (SE 2.3) kg/m 2 , 54.0% men, prevalence of diabetes 59.6%]. The pooled prevalence of advanced fibrosis (≥ F3) was 42.1%. By the rule-out cutoff, the overall sensitivity and specificity were 88% (95% CI: 81-93%; I2 = 89.2%) and 65% (95% CI: 54-75%; I2 = 97.6%), respectively. By the rule-in cutoff, the overall sensitivity and specificity were 68% (95% CI: 57-78%; I2 =91.1%) and 87% (95% CI: 80%-92%; I2 =96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age ( p < 0.01), body mass index ( p < 0.01), and, although not statistically significant, sex ( p = 0.06)., Conclusions: Our systematic review and meta-analysis suggests that Agile 3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Studies have demonstrated a prognostic role of sarcopenia (i.e., loss of skeletal muscle volume and functionality) in patients with various cancer types. In patients with biliary tract cancer, the quantity and quality of skeletal muscles and their serial changes have not been fully investigated in relation to survival outcomes., Methods: We identified 386 patients with unresectable or recurrent biliary tract cancer and calculated skeletal muscle index (SMI) and skeletal muscle density (SMD) to estimate muscular quantity and quality, respectively, based on computed tomography images. Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) according to skeletal muscle status and its serial change., Results: Compared to patients without sarcopenia, patients with sarcopenia were associated with shorter PFS (multivariable HR, 1.60; 95% CI, 1.15-2.22; P = 0.005), but not with OS (P = 0.027) at the adjusted α level of 0.013. SMD at baseline was associated with OS (multivariable HR comparing the extreme quartiles, 1.52; 95% CI, 1.07-2.14; P trend  = 0.012), but not with PFS (P trend  = 0.13). A reduction in SMI rather than that in SMD was associated with OS. Progressive disease was a risk factor for reductions in SMI and SMD., Conclusions: Skeletal muscle quantity and quality and their serial changes were associated with survival outcomes in patients with advanced biliary tract cancer. Our data highlight the importance of designing nutritional and physical interventions for improvements in skeletal muscle status., (© 2024. The Author(s).)