Non-liver-related mortality in the DAA era: Insights from post-SVR patients with and without previous HCC history.

BACKGROUND AND AIMS: Mortality after sustained virological response (SVR) with interferon-free direct-acting antiviral (IFN-free DAA) therapy is crucial for optimizing post-SVR patient care, but it remains unclear, especially regarding non-liver-related mortality. METHODS: Consecutive post-SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person-years [/1000PY]) post-SVR. Mortality rates were compared between cohorts A and B and the general population using age- and sex-adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity-score (PS) matching with sex, age, and comorbidity. RESULTS: In cohort A (n = 762; median age, 65 years), 22 patients died (median follow-up, 36 months); all-cause mortality was 10.0/1000PY, with 86.4% non-liver-related deaths. In cohort B (n = 519; median age, 73 years), 27 patients died (median follow-up, 39 months); all-cause mortality was 16.7/1000PY, with 88.9% non-liver-related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all-cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C (n = 108; median age, 75 years), 15 patients died (median follow-up, 51 months); all-cause mortality was 36.0/1000PY, with 53.3% liver-related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C. CONCLUSIONS: Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non-liver-related deaths in all post-SVR patients.

Investigation of deep learning model for predicting immune checkpoint inhibitor treatment efficacy on contrast-enhanced computed tomography images of hepatocellular carcinoma.

Although the use of immune checkpoint inhibitors (ICIs)-targeted agents for unresectable hepatocellular carcinoma (HCC) is promising, individual response variability exists. Therefore, we developed an artificial intelligence (AI)-based model to predict treatment efficacy using pre-ICIs contrast-enhanced computed tomography (CT) imaging characteristics. We evaluated the efficacy of atezolizumab and bevacizumab in 43 patients at the Nagasaki University Hospital from 2020 to 2022 using the modified Response Evaluation Criteria in Solid Tumors. A total of 197 Progressive Disease (PD), 271 Partial Response (PR), and 342 Stable Disease (SD) contrast CT images of HCC were used for training. We used ResNet-18 as the Convolutional Neural Network (CNN) model and YOLOv5, YOLOv7, YOLOv8 as the You Only Look Once (YOLO) model with precision-recall curves and class activation maps (CAMs) for diagnostic performance evaluation and model interpretation, respectively. The 3D t-distributed Stochastic Neighbor Embedding was used for image feature analysis. The YOLOv7 model demonstrated Precision 53.7%, Recall 100%, F1 score 69.8%, mAP@0.5 99.5% for PD, providing accurate and clinically versatile predictions by identifying decisive points. The ResNet-18 model had Precision 100% and Recall 100% for PD. However, the CAMs sites did not align with the tumors, suggesting the CNN model is not predicting that a given CT slice is PD, PR, or SD, but that it accurately predicts Individual Patient's CT slices. Preparing substantial training data for tumor drug effect prediction models is challenging compared to general tumor diagnosis models; hence, large-scale validation using an efficient YOLO model is warranted.

Recent Advances in Endoscopic Ultrasound for Gallbladder Disease Diagnosis.

Gallbladder (GB) disease is classified into two broad categories: GB wall-thickening and protuberant lesions, which include various lesions, such as adenomyomatosis, cholecystitis, GB polyps, and GB carcinoma. This review summarizes recent advances in the differential diagnosis of GB lesions, focusing primarily on endoscopic ultrasound (EUS) and related technologies. Fundamental B-mode EUS and contrast-enhanced harmonic EUS (CH-EUS) have been reported to be useful for the diagnosis of GB diseases because they can evaluate the thickening of the GB wall and protuberant lesions in detail. We also outline the current status of EUS-guided fine-needle aspiration (EUS-FNA) for GB lesions, as there have been scattered reports on EUS-FNA in recent years. Furthermore, artificial intelligence (AI) technologies, ranging from machine learning to deep learning, have become popular in healthcare for disease diagnosis, drug discovery, drug development, and patient risk identification. In this review, we outline the current status of AI in the diagnosis of GB.

Evolution of Liver Transplantation Over the Last 2 Decades Based on a Single-Center Experience of 300 Cases.

BACKGROUND Over the past 2 decades, there have been many medical advances in the field of liver transplantation. We conducted this study to evaluate the changes in liver transplantation over the last 2 decades. MATERIAL AND METHODS Three hundred cases of liver transplantation encountered between 1997 and 2019 in Nagasaki University Hospital were divided into 3 groups: Era 1 (cases no. 1-100), Era 2 (cases no. 101-200), and Era 3 (cases no. 201-300). Several items were compared among the groups. RESULTS There were no cases of deceased-donor liver transplantation in Era 1, 1 case in Era 2, and 12 cases in Era 3. The proportion of virus-related disease was significantly lower in Era 3 compared to other eras. In contrast, the proportion of alcoholic liver cirrhosis was significantly higher in Era 3 (27%) than Era 1 (7%) and Era 2 (10%) (P<0.01). In Era 1, the right lobe was selected most frequently, but in Eras 2 and 3, the left lobe was more frequently selected. CONCLUSIONS The evolution of the treatment and the transplant system in Japan is clearly reflected in the indications and types of donors for liver transplantation, even at a single center in Japan.

Living donor liver transplantation for a patient with acute liver failure following thyroid storm: a case report.

BACKGROUND: Thyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest. CASE REPORT: The patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications-including intra-abdominal hemorrhaging and ischemic changes in the intestine-her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function. CONCLUSIONS: To our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

Comparison of the novel Franseen needle versus the fine-needle aspiration needle in endoscopic ultrasound-guided tissue acquisition for cancer gene panel testing: A propensity score-matching analysis.

Background and Aim: Reports have indicated that a surface area of 4 mm2 or more of collected tissue sections could provide the recommended total DNA for the OncoGuide NCC Oncopanel system, which is a cancer gene panel test developed in Japan. We wished to compare the percentage of tissue sections collected by endoscopic ultrasound-assisted tissue acquisition (EUS-TA) with surface areas of ≥4 mm2 between a conventional needle, namely the EZ Shot 3 Plus (Olympus Medical Japan, Tokyo, Japan) (EZ3), and the recent SonoTip TopGain (MediGlobe, Rohrdorf, Germany) (TopGain). Method: From April 2010 to December 2021, among 693 EUS-TA cases, EZ3 was used in 390 cases and TopGain in 45. The EZ3 and TopGain groups were matched in a 1:1 ratio with a tolerance of 0.2, with 35 patients each matched using propensity score analysis. Results: The TopGain group had a significantly higher percentage of cases with a tissue area of ≥4 mm2 than the EZ3 group (42.9% vs 68.6%, P = 0.030). Multivariate analysis revealed an association between TopGain and tissue areas of ≥4 mm2 (odds ratio 2.996, 95% confidence interval 1.068-8.403, P = 0.037). Conclusions: EUS-TA using TopGain significantly collected more ≥4 mm2 tissue area compared with EZ3, suggesting its usefulness for cancer gene panel testing.

Hypoglycemia measured by flash glucose monitoring system predicts liver-related events in chronic liver disease patients.

Impaired glucose tolerance, glucose fluctuations, and hypoglycemia have been observed in patients with chronic liver disease (CLD). The flash glucose monitoring (FGM) system, which recognises continuous and dynamic glucose changes in real time, is used in daily clinical practice. This study aimed to examine the association between glucose fluctuations and hypoglycemia, as measured by the FGM system, and liver-related events. Seventy-two patients with CLD and type 2 DM who had their blood glucose measured using Freestyle Libre Pro between April 2017 and July 2018 at our institution were enrolled in this retrospective study. We assessed the results of the FGM system measurements and liver-related events, as defined by gastrointestinal bleeding, infection, ascites, encephalopathy, and liver-related death. The standard deviation (SD) of mean glucose as measured by the FGM system was 41.55 mg/dl, and hypoglycemia was observed in 48.6% (35/72) of the patients. Liver-related event-free survival was not significant when stratified based on SD; however, the event-free survival was significantly lower when stratified by hypoglycemia (p = 0.007). In a multivariate analysis using the Cox proportional hazards model, Child-Pugh class B [Hazards ratio (HR) 2.347 (95% confidence interval (CI): 1.042-5.283), p = 0.039] and hypoglycemia [HR 2.279 (95% CI: 1.064-4.881), p = 0.034] were identified as factors contributing to event-free survival. Hypoglycemia, as determined by the FGM system, was identified as a significant factor that was closely associated with liver-related events. In addition to measuring glucose levels, the FGM system is useful in predicting the occurrence of liver-related events.

Respiratory support with nasal high flow without supplemental oxygen in patients undergoing endoscopic retrograde cholangiopancreatography under moderate sedation: a prospective, randomized, single-center clinical trial.

BACKGROUND: Nasal high flow (NHF) may reduce hypoxia and hypercapnia during an endoscopic retrograde cholangiopancreatography (ERCP) procedure under sedation. The authors tested a hypothesis that NHF with room air during ERCP may prevent intraoperative hypercapnia and hypoxemia. METHODS: In the prospective, open-label, single-center, clinical trial, 75 patients undergoing ERCP performed with moderate sedation were randomized to receive NHF with room air (40 to 60 L/min, n = 37) or low-flow O2 via a nasal cannula (1 to 2 L/min, n = 38) during the procedure. Transcutaneous CO2, peripheral arterial O2 saturation, a dose of administered sedative and analgesics were measured. RESULTS: The primary outcome was the incidence of marked hypercapnia during an ERCP procedure under sedation observed in 1 patient (2.7%) in the NHF group and in 7 patients (18.4%) in the LFO group; statistical significance was found in the risk difference (-15.7%, 95% CI -29.1 - -2.4, p = 0.021) but not in the risk ratio (0.15, 95% CI 0.02 - 1.13, p = 0.066). In secondary outcome analysis, the mean time-weighted total PtcCO2 was 47.2 mmHg in the NHF group and 48.2 mmHg in the LFO group, with no significant difference (-0.97, 95% CI -3.35 - 1.41, p = 0.421). The duration of hypercapnia did not differ markedly between the two groups either [median (range) in the NHF group: 7 (0 - 99); median (range) in the LFO group: 14.5 (0 - 206); p = 0.313] and the occurrence of hypoxemia during an ERCP procedure under sedation was observed in 3 patients (8.1%) in the NHF group and 2 patients (5.3%) in the LFO group, with no significant difference (p = 0.674). CONCLUSIONS: Respiratory support by NHF with room air did not reduce marked hypercapnia during ERCP under sedation relative to LFO. There was no significant difference in the occurrence of hypoxemia between the groups that may indicate an improvement of gas exchanges by NHF. TRIAL REGISTRATION: jRCTs072190021 . The full date of first registration on jRCT: August 26, 2019.

Fully covered metallic stents for anastomotic biliary strictures after living donor liver transplantation.

Objectives: Anastomotic biliary strictures (ABSs) are common complications following living donor liver transplantation (LDLT). We evaluated the feasibility of a novel removable, intraductal, fully covered, self-expandable metallic stent (FCSEMS) for the treatment of ABSs following LDLT. Methods: Nine patients with duct-to-duct ABSs that developed following LDLT were prospectively enrolled in this study. We placed a short FCSEMS with a long lasso and middle waist formation in each patient's ABS above the papilla and removed it 16 weeks later. Results: The FCSEMS placements were successful in all nine cases. Four patients experienced mild cholangitis, which was resolved with conservative treatment. Additionally, there was one case of distal migration. The FCSEMSs were successfully removed from all the patients, and the clinical success rate was 100%. Stricture recurrence occurred in one (11.1%) patient during the follow-up period. Limitations: The small number and lack of comparison with other types of FCSEMSs and plastic stents. Conclusions: Intraductal placement of FCSEMSs is useful for treating refractory ABSs after LDLT, although further studies are required with larger sample sizes.

Peripheral lymphocyte fluctuation as an indicator of severe immune-related adverse events in patients treated with immune checkpoint inhibitors.

AIM: Immune checkpoint inhibitors (ICIs) have proven to be effective treatments for various cancers, but can also elicit immune-related adverse events (irAEs). Given that severe irAEs can be life-threatening, biomarkers that can predict the occurrence of irAEs are of paramount importance. ICIs affect the dynamics of lymphocytes, and alterations in these dynamics may play a role in the development and severity of irAEs. The aim of this study was to investigate the correlation between irAEs and changes in lymphocyte counts. METHODS: Information on irAEs was collected from 226 ICI cases from 2014 to 2020. We compared lymphocyte counts before treatment and at the onset of irAE and investigated the association between lymphocyte count fluctuations and the presence and severity of irAE, the course after steroid treatment, and overall survival. RESULTS: Of the 226 cases, 27 patients developed grade 3 or higher irAE. Compared to the other groups, the lymphocyte count in this group was significantly decreased at the time of irAE (p < 0.01). There was a trend toward a rapid increase in lymphocyte count in the steroid responder group compared to the non-responder group. Regarding overall survival, patients with irAE had significantly longer survival than those without irAE (p = 0.0025). However, there was no association between changes in lymphocyte count and survival in patients with irAE. CONCLUSION: The percentage change in lymphocyte count was found to correlate with the incidence of severe irAEs. Close monitoring of the patient's condition is crucial when the lymphocyte count decreases during ICI treatment.

Evans' syndrome induced by atezolizumab plus bevacizumab combination therapy in advanced hepatocellular carcinoma.

An 86-year-old man presented with recurrence of hepatocellular carcinoma (HCC) after surgery. Atezolizumab plus bevacizumab was initiated. After the third course of atezolizumab plus bevacizumab therapy, petechial purpura appeared on the extremities and trunk. Laboratory tests revealed isolated severe thrombocytopenia without evidence of combined coagulopathy. He was diagnosed with immune thrombocytopenic purpura (ITP), and high-dose immunoglobulin and Helicobacter pylori eradication therapies were administered. Improvement in thrombocytopenia was observed; however, 20 days after the onset of ITP, laboratory data revealed hemolytic anemia. Both direct and indirect Coombs tests were positive, and he was diagnosed with Evan's syndrome complicated by ITP and autoimmune hemolytic anemia (AIHA) induced by immune-related adverse events (irAEs). After treatment with prednisolone, the hemoglobin level increased, and hemolytic findings improved on blood tests. We encountered a rare case of Evans' syndrome due to atezolizumab plus bevacizumab therapy for HCC. In atezolizumab plus bevacizumab therapy, hematologic toxicities are not rare adverse events and attention is required.

EUS-guided fine-needle biopsy sampling of solid pancreatic tumors with 3 versus 12 to-and-fro movements: a multicenter prospective randomized controlled study.

BACKGROUND AND AIMS: A novel EUS-guided fine-needle biopsy sampling (EUS-FNB) needle enabled physicians to obtain sufficient pathologic samples with fewer to-and-fro movements (TAFs) within the lesion. We compared the diagnostic yields of EUS-FNB with 3 and 12 TAFs at each puncture pass. METHODS: The primary endpoint of this multicenter, noninferiority, crossover, randomized controlled trial involving 6 centers was diagnostic sensitivity. Secondary endpoints were diagnostic accuracy and quantity and quality evaluation of EUS-FNB specimens. Length of the macroscopically visible core (MVC) and microscopic histologic quantity were used for quantitative evaluation. Macroscopic visual and microscopic histologic evaluations were performed for qualitative evaluation. RESULTS: Among 110 patients (220 punctures, 110 for 3 TAFs and 12 TAFs each), 105 (210 punctures) had malignant histology. Diagnostic sensitivity for malignancy of 3 TAFs (88.6%) was not inferior to that of 12 TAFs (89.5%; difference, -.9%; 95% confidence interval, -9.81 to 7.86). Diagnostic accuracy for malignancy was 92.7% for 3 TAFs and 94.6% for 12 TAFs. Overall median MVC length was 13.5 mm in both groups. The 3-TAF group had a significantly higher rate of score ≥3 on macroscopic visual quality evaluation than the 12-TAF group (71.8% vs 52.7%, P = .009). No significant intergroup differences existed in microscopic histologic quantity and quality evaluations (quantity evaluation, 88.2% for 3 TAFs vs 83.6% for 12 TAFs; quality evaluation, 90.0% for 3 TAFs vs 89.1% for 12 TAFs). CONCLUSIONS: Diagnostic sensitivity and accuracy of EUS-FNB with 3 TAFs were not inferior to those with 12 TAFs for solid pancreatic lesions. The 3-TAF group showed significantly less blood contamination in sampled tissues than the 12-TAF group. (Clinical trial registration number: UMIN000037309.).

Regular protocol liver biopsy is useful to adjust immunosuppressant dose after adult liver transplantation.

INTRODUCTION: Adjusting immunosuppression to minimal levels post-adult liver transplantation (LT) is critical; however, graft rejection has been reported in LT recipients with normal liver function evaluated by liver biopsy (LBx). Continual protocol liver biopsy (PLB) is performed regularly in LT recipients with normal liver function in some centers; however, its usefulness remains inadequately evaluated. This study aimed to assess retrospectively the usefulness of late PLB after adult LT. METHODS: LBx evaluations of LT recipients with normal liver function and hepatitis B and C virus seronegativity were defined as PLB. The cases requiring immunosuppressive therapy for rejection findings based on Banff criteria were extracted from the PLBs, and pathological data collected before and after immunosuppressive dosage adjustment (based on modified histological activity index [HAI] score) were compared. RESULTS: Among 548 LBx cases, 213 LBx in 110 recipients fulfilled the inclusion criteria for PLB. Immunosuppressive therapy after PLB was intensified in 14 LBx (6.6%) recipients (12.7%); of these, nine had late-onset acute rejection, three had isolated perivenular inflammation, one had plasma cell-rich rejection, and one had early chronic rejection. Follow-up LBx after immunosuppressive dose adjustment showed improvement in the modified HAI score grading in 10 of 14 cases (71.4%). No clinical background and blood examination data, including those from the post-LT period, immunosuppressant trough level, or examination for de novo DSA, predicted rejection in PLB. Complications of PLB were found in only three cases. CONCLUSION: PLB is useful in the management of seemingly stable LT recipients, to discover subclinical rejection and allow for appropriate immunosuppressant dose adjustment.

Clinical features of patients with chronic liver disease in Japan related to alcohol use: Nationwide examination using alcohol use disorders identification test.

AIM: Patients often do not respond truthfully to physicians' interviews concerning alcohol. Few reports regarding the level of alcohol dependence in patients with chronic liver disease (CLD) have been presented. This study aimed to elucidate severity distribution in patients with CLD using the alcohol use disorders identification test (AUDIT). METHODS: From March to June 2022, 2034 Japanese outpatients with CLD, including 415 cases associated with hepatitis C virus, 436 with hepatitis B virus, 173 with alcohol-related liver disease (ARLD), and 1010 with other factors, were interviewed using AUDIT. Clinical features related to alcohol use in these patients were then retrospectively evaluated. RESULTS: In all patients, an AUDIT score 8-14 (harmful use) was noted in 5.8% of hepatitis C virus, 8.9% of hepatitis B virus, 24.3% of ARLD, and 4.4% of other groups, respectively (P < 0.001), while a score ≥15 (dependency) was noted in 3.4%, 3.0%, 27.7%, and 1.9%, respectively (P < 0.001). When the country was divided into regions, the percentages remained similar. Comparisons between patients with and without an AUDIT score ≥8 (n = 1412), performed after exclusion of those without related data (n = 622), showed no significant differences for hepatic reserve function, while those with harmful alcohol use were significantly younger (66 vs. 70 years, P = 0.006) and had a larger percentage of men (80.4% vs. 45.1%, P < 0.001). CONCLUSION: Harmful alcohol and alcohol dependency were observed in approximately 10% of patients with viral or non-viral CLD, after excluding patients with ARLD. Assessment of alcohol intake by use of the AUDIT questionnaire as well as adequate intervention should be considered necessary.

Most Cases of Cryptogenic Cirrhosis May Be Nonobese Nonalcoholic Steatohepatitis - Risk Factors of Liver Steatosis After Liver Transplantation for Cryptogenic Cirrhosis: A Retrospective Study.

Objective The course of cryptogenic cirrhosis (CC) after liver transplantation (LT) is unknown. We therefore clarified the natural course post-LT for CC and investigated the etiology of CC. Methods Eighteen patients who underwent LT for CC were included. To rule out the possibility of nonalcoholic steatohepatitis (NASH) in patients with CC, those with a history of obesity or liver steatosis found pretransplantation were excluded. A liver biopsy was performed one year after LT and annually thereafter. Results Liver steatosis and steatohepatitis were identified in 61% and 39% of patients after LT, respectively, with a median time to the onset of 12 and 27 months, respectively. There were no other pathological findings such as liver allograft rejection, autoimmune hepatitis, or primary biliary cholangitis. The body mass index after LT (28.5 vs. 22.4 kg/m2; p=0.002) and mean muscle attenuation at the time of LT were significantly higher (33.3 vs. 25.8 Hounsfield units, p=0.03) and the postoperative hospitalization period shorter (50 vs. 102 days; p=0.02) in the steatosis group than in the non-steatosis group. Recipients were significantly younger in the steatohepatitis subgroup than in the simple steatosis subgroup (55.0 vs. 63.5 years old; p=0.04). Conclusion Despite excluding CC patients with a history of obesity, we observed that patients with CC had a high prevalence of steatosis after LT than those without CC. Young patients with a favorable postoperative course were noted to have a high risk of NASH after LT for CC. Patients with CC may represent cases of non-obese NASH.

Long-term Outcomes and Prognostic Factors of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma.

BACKGROUND/AIM: This study was conducted to determine the prognosis and risk factors for survival in patients treated with stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This retrospective study analyzed 73 patients who underwent SBRT for HCC at Nagasaki University Hospital from December 2012 to July 2019 and examined the relationship between baseline information and prognosis. The Kaplan-Meier analysis and log-rank test were used to estimate the survival rate. Cox regression analysis was performed to determine the factors associated with overall survival (OS) after SBRT. RESULTS: The 1- and 2-year local control rates were 98.6% and 89.9%, respectively. Survival rates at 1, 3, and 5 years were 94.5%, 63.9%, and 45.5%, respectively. In the univariate analysis, baseline modified albumin-bilirubin grade (mALBI grade) [2b/3, hazard ratio (HR)=2.762, p=0.001], tumor size (≥2 cm, HR=2.479, p=0.003), and Barcelona Clinic Liver Cancer stage (BCLC) (B/C, HR=3.284, p<0.001) were significantly associated with poor prognosis. In multivariate analysis, baseline mALBI grade (2b/3, HR=2.283, p=0.009) and BCLC stage (B/C, HR=2.330, p=0.013) were significantly associated with poor prognosis. Only three patients (4.1%) developed grade 3 adverse events related to SBRT. CONCLUSION: SBRT is effective and safe in patients with HCC. The baseline mALBI grade is useful for predicting patient prognosis after SBRT. Patients with an mALBI grade of 1/2a are expected to have a better prognosis than patients with an mALBI grade of 2b/3.

Long-term outcomes of living-donor liver transplantation, hepatic resection, and local therapy for hepatocellular carcinoma with three <3-cm nodules in a single institute.

Background and Aim: Treatment for small hepatocellular carcinoma (HCC) is determined based on the results of a liver function test and the tumor location and spread. The present study compared the outcomes among local therapy, hepatic resection (HR), and living-donor liver transplantation (LDLT) for small HCC in a single institute. Methods: We compared the overall survival, recurrence-free survival, and cancer-specific survival rates in patients with three HCC nodules <3 cm in size among local therapy, which included radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial chemoembolization (TACE), and surgical treatment (HR and LDLT). Results: One hundred and ninety-seven patients with local therapy (109 RFA, 26 PEI, and 78 TACE), 107 with HR, and 66 with LDLT were enrolled in this study. There was no significant difference in OS among these groups. The recurrence-free, cancer-specific survival (CSS) of LDLT was superior to local therapy and HR. The prognostic factors for the survival were Child-Pugh (CP) Grade B and tumor marker for local therapy and multiple tumors and elevated ALT levels for HR. Conclusions: For CP grade B patients with HCC of three <3-cm nodule, LDLT could be considered because it resulted in better survival and CSS rates than local therapy.

Initial and advanced endoscopic findings of monomorphic epitheliotropic intestinal T-cell lymphoma in the duodenum: A case report.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an aggressive malignant digestive system lymphoma. We report the case of a 68-year-old Asian woman who was diagnosed with MEITL of the duodenum and small intestine due to intestinal obstruction. MEITL is mainly located in the small intestine, and duodenal lesions are rare. Therefore, the endoscopic appearance of MEITL in the duodenum has been reported in only a few cases. In this case, we observed the initial and advanced endoscopic findings of MEITL in the duodenum. The initial findings were only slight mucosal changes; therefore, careful observation is required to detect early-stage MEITL.

The Usefulness of the Athens Insomnia Scale for Evaluating Sleep Disturbance in Patients with Chronic Liver Disease Comparing with Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale.

Background and Objectives: Sleep disturbance due to muscle cramps or hepatic encephalopathy in patients with chronic liver disease (CLD) can lead to a reduced quality of life. The Pittsburgh sleep quality index (PSQI) is commonly used for evaluating sleep disturbance; however, this questionnaire is time-consuming owing to the large number of questions. As the usefulness of the Athens insomnia scale (AIS) in patients with CLD is not sufficiently known, the present study aimed to determine whether the AIS and Epworth sleepiness scale (ESS) could be used as simple alternative questionnaires for evaluating sleep disturbances in patients with CLD. Materials and Methods: A total of 117 patients with CLD were retrospectively evaluated. Patients with overt hepatic encephalopathy were excluded. All patients were examined using the AIS, PSQI, and ESS, and their responses to these questionnaires were statistically analyzed. Results: The number of patients diagnosed with sleep disturbance using the AIS, PSQI, and ESS were 39 (33.3%), 37 (31.6%), and 9 (7.7%), respectively. There was no correlation between PSQI and ESS scores (r = 0.011, p = 0.910); in contrast, the AIS scores showed a significant correlation with the PSQI scores (r = 0.689, p < 0.001). When the PSQI was considered as the standard for evaluating sleep disturbance, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the AIS were 76.9%, 91.0%, 81.1%, and 88.8%, respectively. In the sleep medication group, the sensitivity, specificity, PPV, and NPV of the AIS were 100%, 70%, 78.6%, and 100%, respectively. Conclusions: This is the first report to indicate that the AIS is an alternative questionnaire to the PSQI and that it can be a useful tool for detecting cirrhosis-related complications in patients with CLD.

Automated fibrosis phenotyping of liver tissue from non-tumor lesions of patients with and without hepatocellular carcinoma after liver transplantation for non-alcoholic fatty liver disease.

BACKGROUND: Fibrosis is the most important pathological feature in predicting development of Hepatocellular carcinoma (HCC). However, the incidence rate of HCC in patients with non-alcoholic fatty liver disease (NAFLD) is relatively low. We evaluated phenotypic histological features to differentiate HCC from non-HCC in patients with non-tumor lesions of cirrhotic livers. METHODS: Seventeen patients with NAFLD who underwent liver transplantation were enrolled. FibroNest was used to quantify histological phenotypes of non-tumor fibrosis lesions. Quantification included collagen content and structure traits, fiber morphometric traits, and fibrosis architecture traits. Each trait was described by up to seven quantitative fibrosis traits (qFTs). Among the qFTs measured in each specimen, those that described most of the variability between consecutive groups were automatically detected and combined into a normalized Phenotypic Composite Fibrosis Score (Ph-CFS). We trained FibroNest to identify the principal traits that differentiate HCC from non-HCC. RESULTS: HCC was found in 8 cases and non-HCC in 9 cases. The Ph-CFS significantly differentiated HCC from non-HCC (4.6 vs. 5.9, p < 0.05). Individual qFTs for morphometric features including collagen fiber length, width, perimeter, and area denoted significant differences between HCC and non-HCC. The Ph-CFS could be used to distinguish HCC (Ph-FCS < 5.0) from non-HCC (Ph-FCS ≥ 5.0) with 75% sensitivity and 100% specificity. CONCLUSION: In patients who underwent liver transplantation, fibrotic histological phenotypes in non-tumor lesions appeared to be different between HCC and non-HCC. Phenotypic analysis of collagen in non-tumor lesions might be an effective and automated method to distinguish HCC from non-HCC on histopathology imaging.