New nomenclature and subclassification of steatotic liver disease and loss of skeletal muscle mass: A longitudinal cohort study.

AIMS: Identifying risk factors for sarcopenia is important due to its significant effect on health. The association between sarcopenia and the newly proposed steatotic liver disease (SLD) and its subclassification has largely been unexplored. METHODS: This longitudinal cohort study included 67 905 adults who underwent at least two health checkup examinations. SLD participants were categorized as cryptogenic SLD, metabolic dysfunction-associated SLD, metabolic dysfunction-associated alcoholic liver disease, or alcoholic liver disease. Appendicular skeletal muscle mass (ASM) was evaluated by bioelectrical impedance analysis. RESULTS: The average duration of follow-up was 5.9 years. The annual ASM change was -31.0 g (95% CI -32.3, -29.6) and -38.3 g (-40.3, -36.3) in participants without and with SLD, respectively. When assessed based on SLD severity, annual ASM loss was fastest in SLD participants with Fibrosis-4 score ≥1.3, followed by those with Fibrosis-4 score <1.3 and those without SLD. In multivariable adjusted analysis, annual ASM loss was fastest in participants with metabolic dysfunction-associated alcoholic liver disease (-49.8 g; -93.1, -6.5), followed by those with metabolic dysfunction-associated SLD (-24.7 g; -60.4, 11.1), and alcoholic liver disease (-24.4 g; -91.1, 42.3), and slowest in those with cryptogenic SLD (reference). This pattern was more pronounced in participants with Fibrosis-4 score ≥1.3. CONCLUSION: The loss of skeletal muscle mass was fastest in the participants with metabolic dysfunction-associated alcoholic liver disease, followed by participants with metabolic dysfunction-associated SLD, alcoholic liver disease, and cryptogenic SLD. Particular attention to prevent sarcopenia should be given to SLD patients with cardiometabolic risk factors or alcohol consumption, especially in patients with advanced fibrosis.

Risk of Hepatocellular Carcinoma by Steatotic Liver Disease and Its Newly Proposed Subclassification.

Introduction: Steatotic liver disease (SLD) is a new overarching term proposed to replace nonalcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease. Subclassification includes metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. This study aimed to investigate whether SLD and its subclassification could stratify hepatocellular carcinoma (HCC) risk. Methods: A cohort of 85,119 adults without viral hepatitis or heavy alcohol intake was analyzed for the risk of HCC according to SLD and its subclassification. The fibrosis-4 (FIB-4) index was used to estimate the degree of liver fibrosis. Results: During a median follow-up of 11.9 years, HCC was diagnosed in 123 individuals. The incidence rate of HCC per 1,000 person-years was higher in individuals with SLD than in those without SLD (0.197 vs. 0.071, p < 0.001), with an adjusted hazard ratio of 2.02 (95% confidence interval: 1.40-2.92). The HCC incidence rate per 1,000 person-years was 0, 0.180, and 0.648 for cryptogenic SLD, MASLD, and MetALD, respectively. When participants with SLD was further stratified by the FIB-4 index, the HCC incidence rate per 1,000 person-years was 0.074 for SLD with FIB-4 < 1.3 and 0.673 for SLD with FIB-4 ≥ 1.3. Of note, HCC risk was substantially high (HCC incidence rate: 1.847 per 1,000 person-years) for MetALD with FIB-4 ≥ 1.3. Conclusions: HCC risk was different by SLD and its subclassification. The utilization of SLD and its subclassification can aid in stratifying HCC risk and facilitate the identification of individuals requiring interventions to mitigate the risk of HCC.

Hepatocellular carcinoma outcomes and potential implications for surveillance in elderly patients.

International liver societies recommend hepatocellular carcinoma (HCC) surveillance for those at high-risk of developing HCC. While previous studies have shown the benefits of surveillance for middle-aged patients, but its necessity for elderly patients is unclear. This study aimed to assess the benefits of HCC surveillance in the elderly by comparing diagnosis mode of HCC. Consecutive, elderly patients aged 75 years or older who were newly diagnosed with HCC were screened at our institution between January 2009 and December 2021. Patients were grouped into those who were diagnosed with HCC during surveillance (n = 235, surveillance group) and those who were diagnosed with HCC due to symptoms (n = 184, symptomatic group). The study outcome was overall survival. It was compared in the overall cohort and a propensity score (PS)-matched cohort. Early-stage diagnosis was more frequent in the surveillance group than in the symptomatic group (mUICC stage I/II: 72.3% vs. 39.1%, p < 0.001). The overall survival rate was better in the surveillance group than in the symptomatic group (median 4.4 vs. 2.1 years, log-rank p < 0.001). In multivariable-adjusted models, the hazard ratio (HR) of mortality of the surveillance group compared to the symptomatic group was 0.64 (95% confidence interval (CI): 0.47-0.87). However, further adjustment for the tumor stage markedly attenuated this association, which was no longer statistically significant (adjusted HR = 0.75; 95% CI: 0.54-1.02). In the PS-matched cohort analysis, outcomes were similar when the PS matching variables included the tumor stage. In contrast, when PS matching variables did not include the tumor stage, outcomes were better for the surveillance group. The surveillance group of elderly patients showed better survival than the symptomatic group, which was largely explained by earlier tumor stage at diagnosis. This suggests that the overall outcome of elderly HCC patients could be improved by increasing surveillance-detected cases compared to symptom-driven cases.

Massive Transfusion Protocol and Outcome of Patients with Acute Variceal Bleeding.

Background/Aims: The massive transfusion protocol (MTP) can improve the outcomes of trauma patients with hemorrhagic shock and some patients with non-traumatic hemorrhagic shock. However, no information is available regarding whether MTP can improve the outcomes of acute variceal bleeding (AVB). This study aimed to determine the effects of MTP on the outcomes of patients with AVB. Methods: Consecutive patients (n = 218) with AVB who did not have current malignancy and visited the emergency room between July 2014 and June 2022 were analyzed. 42-day mortality and failure to control the bleeding were compared between patients with and without MTP activation. Additionally, propensity-score matching was conducted. Results: The amount of blood product transfused was higher in the MTP group. The 42-day mortality rate (42.1% vs. 1.5%, p < 0.001) and the rate of failure to control bleeding (36.8% vs. 0.5%, p < 0.001) were significantly higher in those who received blood transfusions by MTP. MTP was an independent factor associated with 42-day mortality in the multivariable-adjusted analysis (HR 21.05; 95% CI 3.07-144.21, p = 0.002, HR 24.04; 95% CI 3.41-169.31, p = 0.001). The MTP group showed consistently higher 42-day mortality and failure to control bleeding in all subgroup analyses, stratified by systolic blood pressure, hemoglobin level, and the model for end-stage liver disease score. The MTP group also showed higher 42-day mortality (42.9% vs. 0%, p = 0.001) and failure to control bleeding (42.9% vs. 0%, p = 0.001) in a propensity score-matched analysis (n = 52). Conclusions: MTP was associated with poor outcomes in patients with AVB. Further studies are needed to see whether MTP can be an option for patients with massive AVB.

Prevalence and predictors of multidrug-resistant bacteremia in liver cirrhosis.

BACKGROUND/AIMS: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. METHODS: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. RESULTS: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). CONCLUSION: More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

Steatotic liver disease and its newly proposed sub-classifications correlate with progression of the coronary artery calcium score.

BACKGROUND & AIMS: A new nomenclature, Steatotic Liver Disease (SLD), has been proposed by consensus with sub-classifications and requires evidence-based validation. We assessed whether the presence and severity of SLD, as well as its sub-classifications, are associated with the progression of coronary atherosclerosis. METHODS: This longitudinal cohort study included 13,811 adults who participated in repeated regular health screening examinations between January 1, 2004 and December 31, 2021 that included assessments of their coronary artery calcium (CAC) scores. SLD was defined using abdominal ultrasonography and classified as metabolic dysfunction associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. SLD severity was assessed using fibrosis-4 (FIB-4) scores. The progression of CAC scores was measured using multidetector CT scans. RESULTS: The average duration of follow-up was 5.8 years. During follow-up, the annual rate of CAC progression in participants with and without SLD was 18% (95% CI 17%-19%) and 14% (95% CI 13%-14%) (p < 0.01), respectively. The multivariable ratios of progression rates when we compared participants with cryptogenic SLD, MASLD, or MetALD with those without SLD were 0.98 (95% CI 0.95-1.01), 1.03 (95% CI 1.03-1.04), and 1.07 (95% CI 1.04-1.09), respectively. The multivariable ratios of progression rates when we compared participants with SLD with FIB-4 score <1.3 and SLD with FIB-4 score ≥1.3 with those without SLD were 1.03 (95% CI 1.02-1.04), and 1.05 (95% CI 1.04-1.06), respectively. CONCLUSIONS: SLD was associated with a higher risk of coronary atherosclerosis, and the risk differed by sub-classifications and severity. These findings suggest that the newly proposed definition has clinical relevance in terms of stratifying cardiovascular disease risk.

Clinicopathologic and Endosonographic Characteristics of Colon Subepithelial Tumors Discovered Incidentally.

BACKGROUND/AIMS: Colonoscopy is commonly used for colorectal cancer screening; therefore, the detection of colon subepithelial tumors (SETs) has also increased. Several research studies have been undertaken to diagnose and treat stomach and rectal SETs. The purpose of this study was to determine a diagnostic point for colon SETs by comparing histological findings with the endoscopic characteristics of colon SETs discovered by chance. METHODS: A total 194 patients underwent an endoscopic ultrasound (EUS) for suspicious colon SETs during a colonoscopy from May 2014 to December 2021. A total of 105 colon SETs, which were histologically diagnosed, were finally included. Fisher's exact test was used to determine the factors associated with malignant SETs. RESULTS: Colon SETs were predominantly present in the right colon (n = 73, 69.5%), particularly in the transverse colon (n = 32, 30.5%). The majority were smaller than 10 mm (n = 88, 83.8%), and they had hard consistencies (n = 84, 80%) and exhibited no surface changes (n = 96, 91.4%). Most of them were found in the submucosal layers (n = 54, 51.4%) and had a hypoechoic pattern (n = 56, 53.3%) in the EUS. Of the histologically confirmed cases, only three (3/105, 2.9%) were malignant. Most benign lesions were lipomas, suspected parasitic infections, or lesions caused by various inflammatory reactions, including fibrous/fibrocalcific lesions and necrotic nodules. All soft lesions were benign. Two of the three malignant lesions were adenocarcinomas, and the other was lymphoma. For the malignant SETs, there was a statistically significant alteration in the surface of the tumors (p < 0.001), and they were located where the muscularis mucosa layer was included (p = 0.008). The potential malignant SETs, granular cell tumors, and neuroendocrine tumors (NETs) had similar features, such as yellowish hypoechoic masses. Colon NETs were only found in the rectosigmoid junction. Parasitic infections and lesions, resulting in various inflammatory reactions, were observed as pale and hard SETs and mostly revealed as mixed echogenic masses located in the muscularis mucosa, submucosa, or multi-layers in the EUS. CONCLUSION: This study showed that small colon SETs were mostly benign lesions. Despite its rarity, pathological confirmation is crucial in cases where the SET has surface changes and has been located in a position where the muscularis mucosa layer was included on the EUS, due to the risk of malignancy.

Risk factors and management of iatrogenic colorectal perforation in diagnostic colonoscopy: a single-center cohort study.

BACKGROUND AND AIMS: Diagnostic colonoscopy plays a central role in colorectal cancer screening programs. We analyzed the risk factors for perforation during diagnostic colonoscopy and discussed the treatment outcomes. METHODS: We performed a retrospective analysis of risk factors and treatment outcomes of perforation during 74,426 diagnostic colonoscopies between 2013 and 2018 in a tertiary hospital. RESULTS: A total of 19 perforations were identified after 74,426 diagnostic colonoscopies or sigmoidoscopies, resulting in a standardized incidence rate of 0.025% or 2.5 per 10,000 colonoscopies. The majority (15 out of 19, 79%) were found at the sigmoid colon and recto-sigmoid junction. Perforation occurred mostly in less than 1000 cases of colonoscopy (16 out of 19, 84%). In particular, the incidence of perforation was higher in more than 200 cases undergoing slightly advanced colonoscopy rather than beginners who had just learned colonoscopy. Old age (≥ 70 years), inpatient setting, low body mass index (BMI), and sedation status were significantly associated with increased risk of perforation. Nine (47%) of the patients underwent operative treatment and ten (53%) were managed non-operatively. Patients who underwent surgery were often diagnosed with delayed or concomitant abdominal pain. Perforations of rectum tended to be successfully treated with endoscopic clipping. CONCLUSIONS: Additional precautions are required to prevent perforation in elderly patients, hospital settings, low BMI, sedated patients, or by a doctor with slight familiarity with endoscopies (but still insufficient experience). Endoscopic treatment should be actively considered if diagnosis is prompt, abdominal pain absent, and especially the rectal perforation is present.

Supplementation with Angelica keiskei inhibits expression of inflammatory mediators in the gastric mucosa of Helicobacter pylori-infected mice.

Oxidative stress is involved in the pathogenesis of Helicobacter pylori-associated gastric ulceration and carcinogenesis. The oxidant-sensitive transcription factor, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), regulates expression of inflammatory mediators such as interferon γ (IFN-γ), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). These inflammatory mediators increased in gastric mucosal tissues from patients infected with H pylori. Angelica keiskei (AK), a green leafy vegetable, is rich in carotenoids and flavonoids and shows antioxidant and anti-inflammatory activities. Therefore, we hypothesized that AK may protect the gastric mucosa of H pylori-infected mice against inflammation. We determined lipid peroxide abundance, myeloperoxidase activity, expression levels of inflammatory mediators (IFN-γ, COX-2, and iNOS), NF-κB-DNA binding activity, and histologic changes in gastric mucosal tissues. The antioxidant N-acetylcysteine served as the positive control treatment. Supplementation with AK suppressed increases in lipid peroxide abundance, myeloperoxidase activity, induction of inflammatory mediators (IFN-γ, COX-2, and iNOS), activation of NF-κB, and degradation of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor α in gastric mucosal tissue from H pylori-infected mice. Inhibition of H pylori-induced alterations by AK was similar to that by N-acetylcysteine. Taken together, these results suggest that supplementation with AK may prevent H pylori-induced gastric inflammation by inhibiting NF-κB-mediated induction of inflammatory mediators in the gastric mucosa of patients infected with H pylori.