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AIM: Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population. METHODS: From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders. RESULTS: In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis. CONCLUSIONS: In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry with the number UMIN000043798.
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Digital pathology has enabled the noninvasive quantification of pathological parameters. In addition, the combination of digital pathology and artificial intelligence has enabled the analysis of a vast amount of information, leading to the sharing of much information and the elimination of knowledge gaps. Fibrosis, which reflects chronic inflammation, is the most important pathological parameter in chronic liver diseases, such as viral hepatitis and metabolic dysfunction-associated steatotic liver disease. It has been reported that the quantitative evaluation of various fibrotic parameters by digital pathology can predict the prognosis of liver disease and hepatocarcinogenesis. Liver fibrosis evaluation methods include 1 fiber quantification, 2 elastin and collagen quantification, 3 s harmonic generation/two photon excitation fluorescence (SHG/TPE) microscopy, and 4 Fibronest™..ãIn this review, we provide an overview of role of digital pathology on the evaluation of fibrosis in liver disease and the characteristics of recent methods to assess liver fibrosis.
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Aim: After pancreaticoduodenectomy, 20-40% of patients develop steatotic liver disease (SLD), and steatohepatitis can be a problem. Although patatin-like phospholipase domain-containing 3 protein (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms are involved in SLD and steatohepatitis development, whether this is the case after pancreaticoduodenectomy is unclear. Methods and Results: Forty-three patients with pancreatic cancer who underwent pancreaticoduodenectomy at our hospital between April 1, 2018, and March 31, 2021, were included. We extracted DNA from noncancerous areas of residual specimens after pancreaticoduodenectomy and determined PNPLA3 and TM6SF2 gene polymorphisms using real-time polymerase chain reaction. SLD was defined as a liver with an attenuation value of ≤40 HU or a liver-to-spleen ratio of ≤0.9 on computed tomography. We defined high hepatic fibrosis indexes (HFI) instead of steatohepatitis as a Fibrosis-4 index of ≥2.67 or nonalcoholic fatty liver disease fibrosis score of ≥0.675 in patients with SLD. The cumulative incidence of SLD (P = 0.299) and high HFI (P = 0.987) after pancreaticoduodenectomy were not significantly different between the PNPLA3 homozygous and minor allele groups. The incidences of high HFI at 1 year after pancreaticoduodenectomy were 16.8% and 27.0% in the TM6SF2 major homozygous and minor allele groups, respectively, with a significant difference in the cumulative incidence (P = 0.046). Conclusion: The TM6SF2 minor allele may contribute to steatohepatitis development after pancreaticoduodenectomy.
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AIM: Echocardiography is necessary for portopulmonary hypertension diagnosis, and identifying patients with cirrhosis who require it is challenging. In this study, we aimed to investigate the utility of the total bile acid (TBA) levels as a screening tool for identifying patients with decompensated cirrhosis who should undergo echocardiography for portopulmonary hypertension diagnosis. METHODS: We evaluated 135 patients with decompensated cirrhosis who underwent liver transplantation. Subsequently, factors contributing to tricuspid regurgitation pressure gradient (TRPG) elevation (≥30 mmHg) were analyzed using preoperative data, including the TBA levels. RESULTS: The median age of patients was 58 years (61 women), and 45 and 90 patients had Child-Turcotte-Pugh grades of B and C, respectively. The median TRPG level was 21 mmHg, and 17 patients (12.6%) showed TRPG elevation. Multiple logistic regression analysis revealed that elevated TBA (odds ratio 4.322; p = 0.013) and main pulmonary artery diameter ≥33 mm (odds ratio 4.333; p = 0.016) were significantly associated with TRPG elevation. The TBA cut-off value (167.7 µmol/L) showed a high diagnostic performance, with 70.6% sensitivity and 64.4% specificity. Ursodeoxycholic acid (UDCA) administration increased the TBA levels dose-dependently. Analysis stratified by UDCA use revealed that in patients not taking UDCA (n = 59), elevated TBA levels and younger age significantly contributed to TRPG elevation. However, in those taking UDCA (n = 76), this contribution disappeared, suggesting that UDCA consumption reduced TBA levels' efficiency in diagnosing TRPG elevation. CONCLUSIONS: The TBA levels may be a potential screening tool for TRPG elevation; however, caution is warranted when interpreting cases treated with UDCA.
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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.
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Carcinome hépatocellulaire , Apprentissage profond , Tumeurs du foie , Humains , Carcinome hépatocellulaire/imagerie diagnostique , Carcinome hépatocellulaire/traitement médicamenteux , Intelligence artificielle , Inhibiteurs de points de contrôle immunitaires/pharmacologie , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Tumeurs du foie/imagerie diagnostique , Tumeurs du foie/traitement médicamenteux , Tomodensitométrie/méthodes , Résultat thérapeutiqueRÉSUMÉ
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.
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Carcinome hépatocellulaire , Hépatite C chronique , Tumeurs du foie , Humains , Sujet âgé , Antiviraux/usage thérapeutique , Carcinome hépatocellulaire/traitement médicamenteux , Tumeurs du foie/traitement médicamenteux , Tumeurs du foie/étiologie , Hépatite C chronique/traitement médicamenteux , Réponse virologique soutenue , FibroseRÉSUMÉ
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.
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Transplantation hépatique , Humains , Transplantation hépatique/méthodes , Donneur vivant , JaponRÉSUMÉ
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.
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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.
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Hypoglycémie , Maladies du foie , Humains , Glucose , Glycémie , Autosurveillance glycémique , Études rétrospectivesRÉSUMÉ
We retrospectively evaluated the impact of therapeutic modifications of atezolizumab (Atezo) plus bevacizumab (Bev) therapy (Atezo/Bev), including the interruption or discontinuation of both Atezo and Bev, and the reduction or discontinuation of Bev, on the outcome of patients with unresectable hepatocellular carcinoma (uHCC) (median observation period: 9.40 months). One hundred uHCC from five hospitals were included. Therapeutic modifications without discontinuation of both Atezo and Bev (n = 46) were associated with favorable overall survival (median not reached; hazard ratio (HR): 0.23) and time to progression (median: 10.00 months; HR: 0.23) with no therapeutic modification defined as the reference. In contrast, the discontinuation of both Atezo and Bev without other therapeutic modifications (n = 20) was associated with unfavorable overall survival (median: 9.63 months; HR: 2.72) and time to progression (median: 2.53 months; HR: 2.78). Patients with modified albumin-bilirubin grade 2b liver function (n = 43) or immune-related adverse events (irAEs) (n = 31) discontinued both Atezo and Bev without other therapeutic modifications more frequently (30.2% and 35.5%, respectively) than those with modified albumin-bilirubin grade 1 (10.2%) and without irAEs (13.0%). Patients with objective response (n = 48) experienced irAEs more frequently (n = 21) than those without (n = 10) (p = 0.027). Avoiding the discontinuation of both Atezo and Bev without other therapeutic modifications may be the optimal management of uHCC.
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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.
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Inhibiteurs de points de contrôle immunitaires , Tumeurs , Humains , Inhibiteurs de points de contrôle immunitaires/effets indésirables , Tumeurs/traitement médicamenteux , Résultat thérapeutique , Lymphocytes , Stéroïdes , Études rétrospectivesRÉSUMÉ
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.
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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.
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Anémie hémolytique auto-immune , Carcinome hépatocellulaire , Tumeurs du foie , Purpura thrombopénique idiopathique , Thrombopénie , Mâle , Humains , Sujet âgé de 80 ans ou plus , Anémie hémolytique auto-immune/induit chimiquement , Anémie hémolytique auto-immune/traitement médicamenteux , Anémie hémolytique auto-immune/complications , Bévacizumab/effets indésirables , Carcinome hépatocellulaire/traitement médicamenteux , Carcinome hépatocellulaire/complications , Tumeurs du foie/traitement médicamenteux , Tumeurs du foie/complications , Thrombopénie/induit chimiquement , Purpura thrombopénique idiopathique/complications , Purpura thrombopénique idiopathique/diagnostic , Purpura thrombopénique idiopathique/traitement médicamenteuxRÉSUMÉ
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.
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Transplantation hépatique , Humains , Adulte , Immunosuppresseurs/usage thérapeutique , Études rétrospectives , Biopsie , Foie/anatomopathologie , Rejet du greffon/diagnosticRÉSUMÉ
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.
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Transplantation hépatique , Stéatose hépatique non alcoolique , Humains , Adulte d'âge moyen , Stéatose hépatique non alcoolique/complications , Stéatose hépatique non alcoolique/épidémiologie , Stéatose hépatique non alcoolique/chirurgie , Transplantation hépatique/effets indésirables , Transplantation hépatique/méthodes , Études rétrospectives , Cirrhose du foie/épidémiologie , Cirrhose du foie/étiologie , Cirrhose du foie/chirurgie , Facteurs de risque , Obésité/complicationsRÉSUMÉ
Chemically-induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. We aimed to clarify the efficacy of CLiPs for ameliorating fibrosis in a diet-induced nonalcoholic steatohepatitis rat model, since nonalcoholic fatty liver disease is currently recognized as the most common form of chronic liver disease in developed countries. METHODS: Primary mature hepatocytes were isolated from 7-week-old male Wistar rats. To establish CLiPs, isolated hepatocytes were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). As an animal model that reproduces NASH pathophysiology, 6-week-old severe combined immunodeficient (SCID) mice were carefully selected and prepared and fed with choline-deficient, L-amino acid-defined, high-fat diet (HFD). After 12 weeks' HFD feeding, the mice were assigned to continue HFD with or without the administration of rat CLiPs (HFD + CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semi-quantitatively evaluated according to histology. Liver parenchyma and blood samples were collected for biochemical analyses. RESULTS: Rat CLiPs were positive for CK19 and EpCAM were successfully delivered to the liver. At 8 weeks after CLiPs transplantation, the HFD + CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD + CLiPs group, as demonstrated by Azan staining and αSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD + CLiPs group. CONCLUSIONS: The anti-fibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans.
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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.
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Carcinome hépatocellulaire , Tumeurs du foie , Radiochirurgie , Albumines , Bilirubine , Carcinome hépatocellulaire/anatomopathologie , Humains , Tumeurs du foie/anatomopathologie , Pronostic , Radiochirurgie/effets indésirables , Études rétrospectivesRÉSUMÉ
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.
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ABSTRACT: Anti-VEGF drugs, such as tyrosine kinase inhibitors, play an important role in systemic therapy for unresectable hepatocellular carcinoma (uHCC). We examined the effects of sorafenib and lenvatinib on proteinuria and renal function.Patients who were administered sorafenib (nâ=â85) or lenvatinib (nâ=â52) as first line treatment for uHCC from July 2009 to October 2020, were enrolled in this retrospective observational study. A propensity score analysis including 13 baseline characteristics was performed. Eighty four patients were selected (sorafenib, nâ=â42; lenvatinib, nâ=â42) by propensity score matching (one-to-one nearest neighbor matching within a caliper of 0.2). We analyzed changes in estimated glomerular filtration rate (eGFR) during tyrosine kinase inhibitor treatment, as well as the development of proteinuria in both groups. A multivariate analysis was performed to identify predictors of a deterioration of eGFR.At 4, 8, 12, and 16âweeks, ΔeGFR was significantly lower in the lenvatinib group than in the sorafenib group (Pâ<â.05). The lenvatinib group showed a significantly higher frequency of proteinuria than the sorafenib group (30.9% vs 7.1%, Pâ=â.005) and had a higher rate of decrease in eGFR than the sorafenib group (Pâ<â.05). Multivariate analysis revealed that lenvatinib use was the only predictive factor of eGFR deterioration (odds ratio 2.547 [95% CI 1.028-6.315], Pâ=â.043). In cases of proteinuria ≤1+ during lenvatinib treatment, eGFR did not decrease. However, eGFR decreased in the long term (>24âweeks) in patients who have proteinuria ≥2+.Lenvatinib has a greater effect on proteinuria and renal function than sorafenib. In performing multi-molecular targeted agent sequential therapy for uHCC, proteinuria and renal function are important factors associated with drug selection after atezolizumab-bevacizumab combination therapy currently used as the first-line treatment.
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Antinéoplasiques , Carcinome hépatocellulaire , Tumeurs du foie , Antinéoplasiques/effets indésirables , Carcinome hépatocellulaire/induit chimiquement , Carcinome hépatocellulaire/traitement médicamenteux , Humains , Rein/physiologie , Tumeurs du foie/induit chimiquement , Tumeurs du foie/traitement médicamenteux , Phénylurées/effets indésirables , Protéinurie/induit chimiquement , Protéinurie/traitement médicamenteux , Quinoléines , Sorafénib/usage thérapeutiqueRÉSUMÉ
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.