Japanese living donor liver transplantation criteria for hepatocellular carcinoma: nationwide cohort study.

BACKGROUND: Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set. METHODS: The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model. RESULTS: Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors. CONCLUSION: This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy.

Importance of gamma-glutamyl transferase elevation in patients with Fontan-associated liver disease.

AIM: In patients with Fontan-associated liver disease (FALD), gamma-glutamyl transferase (GGT) levels are often elevated, however, its clinical importance is unclear. We investigated the relationship between the clinical course of FALD and GGT levels. METHODS: We enrolled 145 patients with FALD who underwent right-heart catheterization (RHC) and visited our department. Ursodeoxycholic acid (UDCA) was administered to 62 of the patients. Patients with GGT levels <50 and ≥50 U/L were compared. Follow-up RHC was undertaken in 76 patients. Cases in which GGT levels decreased by ≥10% or <50 U/L were defined as improved (n = 33). RESULTS: Patients with GGT levels ≥50 U/L had significantly lower levels of albumin and higher levels of alanine transaminase (ALT) but no significant differences in RHC factors. Over a 4.6-year period, 43.4% showed improvement in GGT levels. Improved cases had significantly lower total bilirubin (1.1 vs. 1.6 mg/dL), AST (22 vs. 28 U/L), and ALT (18 vs. 27 U/L) levels than nonimproved cases (n = 29, p < 0.05), and the change in platelet count (-0.5 vs. -3.0 × 10-4/µL) was significantly lower in the latter (p = 0.03). The improvement rate was significantly higher in UDCA-treated cases (55.2%) with GGT levels ≥50 U/L compared to cases not treated with UDCA (18.2%, p = 0.04). CONCLUSION: In cases of FALD with no improvement in GGT level, the platelet count decreased over time, suggesting progression of fibrosis. Physicians should be aware of the importance of a high GGT level in patients with FALD.

Predicting Therapeutic Intervention for Patients with Quiescent Crohn's Disease Using the Small Bowel Capsule Endoscopy Score.

Introduction: Small bowel (SB) capsule endoscopy (SBCE) is a sensitive modality for screening the entire SB of patients with Crohn's disease (CD); however, the prognostic impact of the results is unclear. We evaluated the ability of the SBCE score to predict therapeutic intervention for patients with CD and SB lesions without clinical symptoms as well as negative C-reactive protein (CRP) levels. Methods: Fifty-six patients who underwent a patency evaluation and had a CD activity index (CDAI) score <150 mg/dL and CRP level <0.5 mg/dL were included. Twenty-one and 35 patients had CD classified as Montreal classifications L1 and L3, respectively. The initial SBCE scores were subsequently grouped according to the presence or absence of intervention based on cutoff values. We examined whether the scores could predict the need for therapeutic intervention at 1 year, 2 years, and 5 years. The CD activity in capsule endoscopy (CDACE) score was used as the SBCE score. Results: The median observation period was 1,326 days. Twenty-one patients received therapeutic intervention. There were significant differences between patients with and without treatment intervention according to the CDACE cutoff value of 420 at 1 year, 2 years, and 5 years. Significant differences between patients with Montreal classification L1 with and without intervention were observed at 1 year and 2 years. The CDACE score was moderately and strongly correlated with the Lewis score and capsule endoscopy CDAI score, respectively (Spearman rank correlation coefficient: ρ = 0.6462 and ρ = 0.9199, respectively; p < 0.0001). Conclusion: A CDACE score ≥420 is predictive of intervention after 1 year for patients with CD, a CDAI score <150, and a CRP level <0.5 mg/dL. A larger study with a prospective design is necessary to validate our findings.

Efficacy of serum leucine-rich alpha-2 glycoprotein in predicting findings of Crohn's disease small bowel lesion in capsule endoscopy.

Background/Aims: Small bowel capsule endoscopy (SBCE) is an evaluation method for small bowel (SB) lesions in Crohn's disease (CD). However, the relationship between SBCE findings and the serological biomarker leucine-rich alpha-2 glycoprotein (LRG) remains unclear. We aimed to establish appropriate cutoff values of LRG to predict the presence of SB lesions in CD through SBCE. Methods: Patients with CD with SB lesions who had undergone SBCE and LRG measurements 1 month before and after the SBCE were included. The LRG values for ulcers ≥0.5 cm and other inflammatory lesions noted in SBCE were determined using the Youden Index, and the sensitivity and specificity were calculated. Additionally, the correlation between the SBCE scores (CD Activity in Capsule Endoscopy) and LRG values was evaluated. Results: Forty patients without active colorectal lesions were included in the study. When the cutoff value of LRG for SB ulcers ≥ 0.5 cm was set at 14 µg/mL, the sensitivity was 92.3%, specificity was 81.5%, positive predictive value (PPV) was 70.6%, and negative predictive value (NPV) was 95.7%. In contrast, an LRG cutoff value of 12 µg/mL without inflammatory findings had a sensitivity of 91.7%, specificity of 82.1%, PPV of 68.8%, and NPV of 95.8%. CD Activity in Capsule Endoscopy correlated well with LRG values (Spearman's rank correlation coefficient ρ = 0.681, P< 0.001). Conclusions: An LRG cutoff value of 14 µg/mL may be useful in predicting the presence of SB ulcers ≥ 0.5 cm, and an LRG cutoff value of 12 µg/mL may be useful in predicting the absence of SB inflammatory findings.

Deep learning and digital pathology powers prediction of HCC development in steatotic liver disease.

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.

Endoscopic Features of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma without Helicobacter pylori.

Although gastric mucosa-associated lymphoid tissue (MALT) lymphoma without Helicobacter pylori (HP) has increased recently, a specific endoscopic classification has not been established; its endoscopic characteristics have not been investigated. In this study, we retrospectively investigated gastric MALT lymphoma without HP in our hospital and assessed differences in the endoscopic findings according to HP infection status. Fifty-seven patients with gastric MALT lymphoma Lugano stage I, diagnosed between January 2013 and March 2023, were divided into three groups (currently HP infected, previously infected, and uninfected), wherein their endoscopic findings were evaluated. Furthermore, the superficial type, as per the classification of Sano et al., was independently subdivided based on the endoscopic differential diagnoses, as follows: atrophic gastritis-like, angiodysplasia-like, superficial gastritis-like, and undifferentiated carcinoma-like. Compared with the currently infected group, the HP-uninfected group tended to have more small lesions without erosion and more discolored, undifferentiated carcinoma-like depressed lesions. In addition, the positive rate of the tree-like appearance (TLA) and ballooning characteristics of gastric MALT lymphoma in magnified findings was lower in the HP-uninfected group. In patients without HP infection, MALT lymphoma should be excluded, even in the absence of suspicious magnifying findings such as TLA or ballooning.

Comparison of Endoscopic and Artificial Intelligence Diagnoses for Predicting the Histological Healing of Ulcerative Colitis in a Real-World Clinical Setting.

Background: Artificial intelligence (AI)-assisted colonoscopy systems with contact microscopy capabilities have been reported previously; however, no studies regarding the clinical use of a commercially available system in patients with ulcerative colitis (UC) have been reported. In this study, the diagnostic performance of an AI-assisted ultra-magnifying colonoscopy system for histological healing was compared with that of conventional light non-magnifying endoscopic evaluation in patients with UC. Methods: The data of 52 patients with UC were retrospectively analyzed. The Mayo endoscopic score (MES) was determined by 3 endoscopists. Using the AI system, healing of the same spot assessed via MES was defined as a predicted Geboes score (GS) < 3.1. The GS was then determined using pathology specimens from the same site. Results: A total of 191 sites were evaluated, including 159 with a GS < 3.1. The MES diagnosis identified 130 sites as MES0. A total of 120 sites were determined to have healed based on AI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MES0 for the diagnosis of GS < 3.1 were 79.2%, 90.6%, 97.7%, 46.8%, and 81.2%, respectively. The AI system performed similarly to MES for the diagnosis of GS < 3.1: sensitivity, 74.2%; specificity: 93.8%; PPV: 98.3%; NPV: 42.3%; and accuracy: 77.5%. The AI system also significantly identified a GS of < 3.1 in the setting of MES1 (P = .0169). Conclusions: The histological diagnostic yield the MES- and AI-assisted diagnoses was comparable. Healing decisions using AI may avoid the need for histological examinations.

Efficacy and safety of tacrolimus in older adults with ulcerative colitis: a retrospective study.

BACKGROUND/AIMS: The prevalence of ulcerative colitis (UC) has been increasing, also in older adults. Here, we retrospectively compared the efficacy and safety of tacrolimus (TAC) in older and younger patients with UC. METHODS: We included younger (age < 65 years; n = 116) and older patients (age ≥ 65 years; n = 21) with UC who received TAC from April 2009 through December 2022(mean follow-up, 1230 ± 175 days) and achieved remission. Evaluations included age at onset, laboratory values, estimated glomerular filtration rate (eGFR), use of 5-aminosalicylic acid (5-ASA), biological experience, colonoscopy scores, remission at 1 month after treatment initiation, and adverse events. Treatment duration and renal function were assessed in patients with follow-up data (younger patients, n = 110; older patients, n = 19). RESULTS: Older patients had a higher age at onset and treatment initiation but less 5-ASA use and biological experience. Before treatment, hemoglobin, albumin, and eGFR were significantly lower in the older group and CRP was significantly higher. The remission rate was 80.1% in the younger group and 66.6% in the older group (P = 0.1862). Adverse events were similar in both groups. The older group had a shorter treatment duration and significantly less change in renal function at all time points. DISCUSSION: Rates of TAC-induced remission and adverse events were similar in older and younger adults with UC. CONCLUSION: TAC can be used safely in elderly patients with moderate to severe UC with careful monitoring.

Serum level of full-length connective tissue growth factor reflects liver fibrosis stage in patients with Fontan-associated liver disease.

BACKGROUND: Chronic liver disease leads to liver fibrosis, and an accurate diagnosis of the fibrosis stage is crucial for medical management. Connective tissue growth factor (CTGF) is produced by endothelial cells and platelets and plays a central role in inducing fibrosis in various organs. In the present study, we tested the validity of measuring the serum levels of two types of CTGF to estimate the biopsy-confirmed liver fibrosis stage. METHODS: We used two detection antibodies targeting the N- and C-terminal of CTGF to measure the serum levels of two forms of CTGF consisting of its full length and its N-terminal fragment. We analyzed the level of CTGF (via enzyme-linked immunosorbent assay) and the liver fibrosis stage in 38 patients with Fontan-associated liver disease (FALD) (26 cases of which were diagnosed pathologically). Correlations were determined by multivariate analysis and the area under the receiver operating characteristic curve. The 65 patients with nonalcoholic fatty liver disease (NAFLD) were included as a disease control group for examination. RESULTS: Full-length CTGF was significantly inversely correlated with liver fibrosis in patients with FALD. Although the platelet count was also associated with the liver fibrosis stage, full-length CTGF was more closely correlated with the fibrosis stage. Furthermore, the level of full-length CTGF was inversely associated with high central venous pressure. Conversely, the serum level of CTGF was not correlated with the fibrosis stage in NAFLD. CONCLUSION: The serum level of full-length CTGF may be useful for estimating the liver fibrosis stage in patients with FALD.

New concept in fatty liver diseases.

In 2023, the nonalcoholic fatty liver disease (NAFLD) Nomenclature Consensus group proposed a new name and concept for NAFLD/nonalcoholic steatohepatitis. The Japanese Society of Gastroenterology and the Japanese Society of Hepatology have accepted these new names and concepts. It was reported that the terms "nonalcoholic" and "fatty" are misleading and inappropriate, because NAFLD does not reflect the etiology. Thus, appropriate disease names are discussed, and new concepts are published. First, the concept of steatotic liver disease (SLD) was proposed to encompass fatty liver diseases of various etiologies, which are classified into five categories. The diagnostic criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) included fatty liver with at least one of the five cardiometabolic risk factors (body mass index or waist diameter, blood glucose or glycated hemoglobin, blood pressure, triglycerides, and high-density lipoprotein cholesterol) and the same restriction of alcohol consumption as NAFLD. A new fatty liver category was described, MetALD, to represent the intermediate drinker group (patients with MASLD with high weekly alcohol intake [140-350 g/week in women and 210-420 g/week in men]). The other five categories are alcohol-associated liver disease, fatty liver with an identifiable specific cause, and other fatty livers of unknown cause. Nonalcoholic steatohepatitis is an important pathological concept (metabolic dysfunction-associated steatohepatitis); however, its definition, including hepatocellular balloon-like degeneration, needs to be reassessed. In Japan, we should use these names and criteria to manage SLD, including hepatocellular carcinoma, which is markedly increasing.

Patlak Reconstruction Using Dynamic 18 F-FDG PET Imaging for Evaluation of Malignant Liver Tumors : A Comparison of HCC, ICC, and Metastatic Liver Tumors.

PURPOSE OF THE REPORT: The aim of this study was to explore the different patterns of dynamic whole-body (D-WB) FDG PET/CT parameters among liver malignancy types as potential diagnostic clues and investigate the association between static and dynamic PET/CT parameters for each tumor histology. PATIENTS AND METHODS: Seventy-one patients with intrahepatic cholangiocarcinoma (ICC), metastatic liver tumor (MLT), or hepatocellular carcinoma (HCC) who underwent D-WB and static dual-time-point FDG PET/CT were enrolled. We obtained Pearson correlation coefficients between the metabolic rate of FDG (MR FDG ; mg/min/ 100ml) or distribution volume of free FDG (DV FDG , %) and static PET/CT parameters. We compared MR FDG and DV FDG values by tumor type and performed receiver operating characteristic analyses for MR FDG and static images. RESULTS: A total of 12 ICC, 116 MLT, and 36 HCC lesions were analyzed. MR FDG and DV FDG showed excellent correlation with early (SUV e ) and delayed SUV max (SUV d ) ( r = 0.71~0.97), but DV FDG in the HCC lesions did not ( r = 0.62 and 0.69 for SUV e and SUV d , respectively) ( P < 0.001 for all). HCC lesions showed significantly lower MR FDG (2.43 ± 1.98) and DV FDG (139.95 ± 62.58) than ICC (5.02 ± 3.56, 207.06 ± 97.13) and MLT lesions (4.51 ± 2.47, 180.13 ± 75.58) ( P < 0.01 for all). The optimal MR FDG could differentiate HCC from ICC and MLT with areas under the curve of 0.84 and 0.80, respectively. Metastatic liver tumor lesions showed the widest distribution of MR FDG and DV FDG values but with no significant difference among most primary sites. CONCLUSIONS: MR FDG was strongly correlated with SUV max in the 3 malignancies and showed utility for differentiating HCC from ICC and MLT. Each tumor type has a different glucose metabolism, and D-WB FDG PET/CT imaging has the potential to visualize those differences.

An Analysis of 10,000 Cases of Living Donor Liver Transplantation in Japan: Special Reference to the Graft-Versus-Recipient Weight Ratio and Donor Age.

OBJECTIVE: To analyze 10,000 cases of living donor liver transplantation (LDLT) recipient data to elucidate outcomes with special reference to the graft-versus-recipient weight ratio (GRWR), based on the Japanese Liver Transplantation Society (JLTS) registry. BACKGROUND: The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT. METHODS: Between November 1989 and August 2021, 10,000 patients underwent LDLT in Japan. The procedures performed during the study period included pediatric liver transplantation (age <18 years, n = 3572) and adult liver transplantation (age ≥18 years, n=6428). Factors related to patient survival (PS) and graft survival (GS) were also analyzed. RESULTS: The GRWR was <0.7, 0.7 to <0.8, 0.8 to <3, 3 to <5, and ≥5 in 0.2%, 2.0%, 61.8%, 31.8%, and 2.6% of pediatric patients and <0.6, 0.6 to <0.7, 0.7 to <0.8, and ≥0.8 in 8.0%, 12.7%, 17.7%, and 61.5% of adult patients, respectively. Among pediatric recipients, the PS rate up to 5 years was significantly better in cases with a GRWR ≤5 than in those with a GRWR >5. When the GRWR and donor age were combined, among adult recipients 50 to 60 years old, the early PS and GS up to 5 years were significantly better in cases with a GRWR ≥0.7, than in those with a GRWR <0.7. (P = 0.02). In adults, a multivariate analysis showed that GRWR <0.6, transplant era (<2011), donor age (>60 years), recipient age (>60 years), model for end-stage liver disease score (≥20), and center volume (<10) were significant prognostic factors for long-term PS. CONCLUSION: Although a satisfactory long-term PS and GS, especially in the recent era (2011-2021), was achieved in the JLTS series, a GRWR ≥5 in pediatric cases and relatively old donors with a GRWR <0.7 in adult cases should be managed with caution.