Association between Atherosclerosis and High-Risk Colorectal Adenomas based on Cardio-Ankle Vascular Index and Ankle-Brachial Index.

Background/Aims: Colorectal adenomas are precancerous lesions that may lead to colorectal cancer. Recent studies have shown that colorectal adenomas are associated with atherosclerosis. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are noninvasive methods for evaluating atherosclerosis. This study examined the association between atherosclerosis and high-risk colorectal adenomas based on the CAVI and ABI. Methods: The data of patients aged ≥50 years who had a colonoscopy and CAVI and ABI measurements from August 2015 to December 2021 at the Kangwon National University Hospital were analyzed retrospectively. After the colonoscopy, subjects were divided into no, overall, and high-risk (size ≥1 cm, high-grade dysplasia or villous adenoma, three or more adenomas) adenoma groups based on the pathology findings. The data were subjected to univariate and multivariate logistic regression analyses. Results: Among the 1,164 subjects, adenomas and high-risk adenomas were found in 613 (52.6%) and 118 (10.1%) patients, respectively. The rate of positive ABI (<0.9) and positive CAVI (≥9.0) were significantly higher in the high-risk adenoma group (22.0% and 55.9%) than in the no adenoma (12.3% and 39.6%) and the overall adenoma group (15.7% and 44.0%) (p=0.008 and p=0.006, respectively). Multivariate analysis revealed a positive CAVI and smoking status to be significantly associated with high-risk adenoma with an odds ratio of 1.595 (95% confidence interval 1.055-2.410, p=0.027) and 1.579 (1.072-2.324, p=0.021), respectively. Conclusions: In this study, a significant correlation between positive CAVI and high-risk adenomas was observed. Therefore, CAVI may be a significant predictor for high-risk colorectal adenoma.

DERIVATION OF A MORTALITY PREDICTION MODEL IN CRITICAL CARE PATIENTS WITH CIRRHOSIS AND SEPSIS.

ABSTRACT: Objective : The aim of the study is to develop a predictive model for in-hospital mortality in critically ill patients with cirrhosis and sepsis, using clinical and laboratory data. Design : This is a retrospective cohort study. Setting: Medical and mixed intensive care units (ICUs) of a tertiary medical center. Patients : Cirrhotic adults were admitted with sepsis to the ICUs from January of 2007 to May of 2017. Interventions : None. Measurements and Main Results : Of 2,595 ICU admissions of patients with cirrhosis, 277 with first ICU admission for sepsis were included in the analysis, and 37% died in the hospital. Patients who stayed in the ICU for at least 6 h (n = 275) were considered for the multivariate model. Ten-fold cross-validation was used to estimate best parameter values and model performance, and the final model was chosen as the model maximizing area under the receiver-operating characteristic curve. Variables in order of impact were Acute Physiology and Chronic Health Evaluation (APACHE) III score, initial serum lactate, conjugated bilirubin, serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin. The final best model from cross-validation presented an area under the receiver operator characteristic curve (AUC) of 0.75, using a cut-point of 50% estimated probability, sensitivity and specificity were 0.46 and 0.90, respectively, with positive predictive value of 0.72 and negative predictive value of 0.74. These results were similar to the APACHE III only model (AUC = 0.74, sensitivity = 0.43, specificity = 0.89, positive predictive value = 0.69, negative predictive value = 0.73). Conclusion : The combination of initial serum lactate level, conjugated bilirubin, initial serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin did not yield meaningful improvement in the AUC and did not provide advantage over the APACHE III score for the prediction of in-hospital mortality in critically ill patients with cirrhosis and sepsis.

Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study.

This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

Phloretin Ameliorates Succinate-Induced Liver Fibrosis by Regulating Hepatic Stellate Cells.

BACKGRUOUND: Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study. METHODS: In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver. RESULTS: Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the activation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis. CONCLUSION: Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.

Outcome of Intermittent Thoracentesis versus Pigtail Catheter Drainage for Hepatic Hydrothorax.

Background/Aims: The management of hepatic hydrothorax (HH) remains a challenging clinical scenario with suboptimal options. We investigated the effect and safety of pigtail catheter drainage compared to intermittent thoracentesis. Methods: This multicenter, retrospective study included 164 cirrhotic patients with recurrent pleural effusion from March 2012 to June 2017. Patients with neoplasms, cardiopulmonary disease, and infectious conditions were excluded. We compared the clinical outcomes of pigtail catheter drainage versus thoracentesis for variables including complications related to procedures, overall survival, and re-admission rates. Results: A total of 164 patients were divided into pigtail catheter (n = 115) and thoracentesis (n = 49) groups. During the follow-up period of 6.93 months after discharge, 98 patients died (pigtail; n = 47 vs. thoracentesis; n = 51). The overall survival (p = 0.61) and 30-day mortality (p = 0.77) rates were similar between the pigtail catheter and thoracentesis groups. Only MELD scores were associated with overall survival (adjusted HR, 1.08; p < 0.01) in patients with HH. Spontaneous pleurodesis occurred in 59 patients (51.3%) in the pigtail catheter group. Re-admission rates did not differ between the pigtail catheter and thoracentesis groups (13.2% vs 19.6% p = 0.7). A total of five complications occurred, including four total cases of bleeding (one patient in the pigtail catheter group and three in the thoracentesis group) and one case of empyema in the pigtail catheter group. Conclusions: Pigtail catheter drainage is not inferior to that of intermittent thoracentesis for the management of HH, proving it may be an effective and safe clinical option.

Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction.

BACKGRUOUND: Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis. METHODS: To clarify the effects and mechanisms of gemigliptin, we conducted various experiments in LX-2 cells (immortalized human hepatic stellate cells [HSCs], the principal effectors of hepatic fibrogenesis), which were activated by succinate and exhibited elevated expression of α-smooth muscle actin, collagen type 1, and pro-inflammatory cytokines and increased cell proliferation. In vivo, we examined the effects and mechanisms of gemigliptin on a high-fat, high-cholesterol-induced mouse model of nonalcoholic steatohepatitis (NASH). RESULTS: Gemigliptin decreased the expression of fibrogenesis markers and reduced the abnormal proliferation of HSCs. In addition, gemigliptin reduced the succinate-induced production of mitochondrial reactive oxygen species (ROS), intracellular ROS, and mitochondrial fission in HSCs. Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction. CONCLUSION: Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease.

The Effects of Irisin on the Interaction between Hepatic Stellate Cell and Macrophage in Liver Fibrosis.

BACKGRUOUND: Hepatic stellate cells (HSCs) are the central players interacting with multiple cell types in liver fibrosis. The crosstalk between HSCs and macrophages has recently become clearer. Irisin, an exercise-responsive myokine, was known to have a potentially protective role in liver and renal fibrosis, especially in connection with stellate cells. This study investigated the effects of irisin on the interaction between HSCs and macrophages. METHODS: Tamm-Horsfall protein-1 (THP-1) human monocytes were differentiated into macrophages, polarized into the inflammatory M1 phenotype with lipopolysaccharide. Lieming Xu-2 (LX-2) cells, human HSCs, were treated with conditioned media (CM) from M1 macrophages, with or without recombinant irisin. HSCs responses to CM from M1 macrophages were evaluated regarding activation, proliferation, wound healing, trans-well migration, contractility, and related signaling pathway. RESULTS: CM from M1 macrophages significantly promoted HSC proliferation, wound healing, transwell migration, and contractility, but not activation of HSCs. Irisin co-treatment attenuated these responses of HSCs to CM. However, CM and irisin treatment did not induce any changes in HSC activation. Further, irisin co-treatment alleviated CM-induced increase of phopho-protein kinase B (pAKT), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1). CONCLUSION: These findings suggested that irisin may play a protective role in the pathogenesis of liver fibrosis, especially when working in the crosstalk between HSCs and macrophages.

High Dose Intramuscular Vitamin D3 Supplementation Impacts the Gut Microbiota of Patients With Clostridioides Difficile Infection.

Background and Aim: Current therapeutic strategies for Clostridioides difficile infections (CDI), including oral vancomycin, metronidazole and fecal microbial transplantation, have limited efficacy and treatment failure may occur in as many as one- third of cases. Recent studies have reported that lower concentrations of 25-hydroxyvitamin D are associated with CDI severity and recurrence. However, there have been no studies on microbiota composition after the administration of vitamin D in patients with CDI. Therefore, our study aimed to compare the microbiota composition between the two groups, including eight CDI-positive patients with vitamin D supplementation and ten CDI-positive patients without vitamin D supplementation by using 16S rRNA microbial profiling. Methods: Twenty subjects were enrolled in this prospective randomized controlled study. One subject dropped out due to lack of contact with the guardian after discharge and one subject dropped out due to withdrawal of consent. Thus, 18 patients with CDI and vitamin D insufficiency (vitamin D level < 17 ng/mL) were divided into two groups: CDI with vitamin D supplementation (n = 8) and CDI without vitamin D supplementation (control: n = 10). Subjects with vitamin D insufficiency were randomized to receive 200,000 IU intramuscular cholecalciferol whereas patients in the control group received only oral vancomycin. Stool samples were obtained twice before vancomycin was administered and eight weeks after treatment; the V3-V4 16S rRNA metagenomic sequencing was performed using EzBioCloud. Results: The alpha diversity of the gut microbiota in the recovery state was significantly higher than that in the CDI state. Analysis of bacterial relative abundance showed significantly lower Proteobacteria and higher Lachnospiraceae, Ruminococcaceae, Akkermansiaceae, and Bifidobacteriaceae in the recovery state. When comparing the control and vitamin D treatment groups after eight weeks, increase in alpha diversity and, abundance of Lachnospiraceae, and Ruminococcaceae exhibited the same trend in both groups. A significant increase in Bifidobacteriaceae and Christensenellaceae was observed in the vitamin D group; Proteobacteria abundance was significantly lower in the vitamin D treatment group after eight weeks than that in the control group. Conclusion: Our study confirmed that the increase in the abundance of beneficial bacteria such as Bifidobacteriaceae, and Christensenellaceae were prominently evident during recovery after administration of a high dose of cholecalciferol. These findings indicate that vitamin D administration may be useful in patients with CDI, and further studies with larger sample sizes are required.

Reappraisal of sepsis-3 and CLIF-SOFA as predictors of mortality in patients with cirrhosis and infection presenting to the emergency department: A multicenter study.

BACKGROUND/AIMS: Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) have been advocated to be used in defining sepsis in the general population. We aimed to compare the Sepsis-3 criteria and Chronic Liver Failure-SOFA (CLIF-SOFA) scores as predictors of in-hospital mortality in cirrhotic patients admitted to the emergency department (ED) for infections. METHODS: A total of 1,622 cirrhosis patients admitted at the ED for infections were assessed retrospectively. We analyzed their demographic, laboratory, and microbiological data upon diagnosis of the infection. The primary endpoint was inhospital mortality rate. The predictive performances of baseline CLIF-SOFA, Sepsis-3, and qSOFA scores for in-hospital mortality were evaluated. RESULTS: The CLIF-SOFA score proved to be significantly better in predicting in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.80; 95% confidence interval [CI], 0.78-0.82) than the Sepsis-3 (AUROC, 0.75; 95% CI, 0.72-0.77, P<0.001) and qSOFA (AUROC, 0.67; 95% CI, 0.64-0.70; P<0.001) score. The CLIF-SOFA, CLIF-C-AD scores, Sepsis-3 criteria, septic shock, and qSOFA positivity were significantly associated with in-hospital mortality (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.19-1.28; aHR, 1.13; 95% CI, 1.09-1.17; aHR, 1.19; 95% CI, 1.15-1.24; aHR, 1.88; 95% CI, 1.42-2.48; aHR, 2.06; 95% CI, 1.55-2.72; respectively; all P<0.001). For CLIF-SOFA scores ≥6, in-hospital mortality was >10%; this is the cutoff point for the definition of sepsis. CONCLUSION: Among cirrhosis patients presenting with infections at the ED, CLIF-SOFA scores showed a better predictive performance for mortality than both Sepsis-3 criteria and qSOFA scores, and can be a useful tool of risk stratification in cirrhotic patients requiring timely intervention for infection.

Relationship Between Etiology of Cirrhosis and Survival Among Patients Hospitalized in Intensive Care Units.

OBJECTIVE: To determine short-term outcomes of patients with alcohol-associated cirrhosis (ALC) admitted to the intensive care unit (ICU) compared with other etiologies of liver disease. In addition, we investigate whether quick sequential organ failure assessment accurately predicts presence of sepsis and in-hospital mortality in critically ill patients with various etiologies of cirrhosis. METHODS: A retrospective cohort of 1174 consecutive patients with cirrhosis admitted to the ICU between January of 2006 and December of 2015 was analyzed. Outcomes of interest included survival rates within the ICU, post-ICU in-hospital, or at 30 days post-ICU discharge. RESULTS: Five hundred seventy-eight patients were found to have ALC with 596 in the non-ALC group. There was no significant difference in ICU mortality rates in ALC versus non-ALC cohorts (10.2% vs 11.7%, P=.40). However, patients with ALC had significantly higher post-ICU in-hospital death (10.0% vs 6.5%, P=.04) as well as higher mortality at 30-day post-ICU discharge (18.7% vs 11.2%, P<.001). Sustained alcohol abstinence did not offer survival advantage over nonabstinence. The predictive power for quick sequential organ failure assessment for sepsis and in-hospital mortality for patients with cirrhosis was limited. CONCLUSION: Critically ill patients with ALC have decreased survival after ICU discharge compared with patients with other etiologies of cirrhosis, independent of alcohol abstinence.

Novel management of expected post-radiotherapy complications in hepatocellular carcinoma patients: a case report.

In recent years, radiotherapy (RT) has been used to treat hepatocellular carcinoma (HCC) at each stage. This clinical trend has developed with the increasing improvement of RT techniques, which show clinical results comparable to those of other treatment modalities. Intensity-modulated radiotherapy uses a high radiation dose to improve treatment effectiveness. However, the associated radiation toxicity can damage adjacent organs. Radiation-induced gastric damage with gastric ulcers is a complication of RT. This report presents a novel management strategy for preventing post-RT gastric ulcers. We present the case of a 53-year-old male patient diagnosed with HCC, who experienced gastric ulcer after RT. Before the second round of RT, the patient was administered a gas-foaming agent, which was effective in preventing RT complications.

Relationship Between Body Mass Index and Survival Among Critically Ill Patients With Cirrhosis.

BACKGROUND: Obesity paradox is a phenomenon in which obesity increases the risk of obesity-related chronic diseases but paradoxically is associated with improved survival among obese patients with these diagnoses. OBJECTIVES: The aim of this study was to explore the obesity paradox among critically ill patients with cirrhosis admitted to the Intensive Care Unit. METHODS: A retrospective cohort of 1,143 consecutive patients with cirrhosis admitted to the ICU between January of 2006 and December of 2015 was analyzed. Primary outcome of interest was in-hospital mortality with secondary end points including ICU and short-term mortality at 30 days post ICU admission. RESULTS: Logistic regression with generalized additive models was used, controlling for clinically relevant and statistically significant factors to determine the adjusted relationship between body mass index (BMI) and ICU, post-ICU in-hospital, and 30 day mortality following ICU discharge. ICU and hospital length of stay was similar across all BMI classes. Adjusted ICU mortality was also similar when stratified by BMI. However, a significant reduction in post-ICU hospital mortality was observed in class I and II obese patients with cirrhosis (BMI 30-39.9 kg/m2) compared to normal BMI (OR = 0.41; 95% CI, 0.20 to 0.83; P = 0.014). Similarly, overweight (BMI 25-29.9 kg/m2) and class I and II obese patients with cirrhosis had significantly lower 30-day mortality following ICU discharge (OR = 0.52, 95% CI 0.31 to 0.87; P = 0.014; OR = 0.50, 95% CI 0.29 to 0.86; P = 0.012, respectively) compared to those with normal BMI. CONCLUSION: The signal of obesity paradox is suggested among critically ill patients with cirrhosis.

Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1.

The Warburg effect is important for cancer cell proliferation. This phenomenon can be flexible by interaction between glycolysis and mitochondrial oxidation for energy production. We aimed to investigate the anticancer effects of the pyruvate dehydrogenase kinase inhibitor, dichloroacetate (DCA) and the mitochondrial respiratory complex I inhibitor metformin in liver cancer cells. The anticancer effect of DCA and/or metformin on HepG2, PLC/PRF5 human liver cancer cell lines, MH-134 murine hepatoma cell lines, and primary normal hepatocytes using MTT assay. Inhibition of lactate/ATP production and intracellular reactive oxygen species generation by DCA and metformin was investigated. Inhibition of PI3K/Akt/mTOR complex I was evaluated to see whether it occurred through AMPK signaling. Anticancer effects of a combination treatment of DCA and metformin were evaluated in HCC murine model. The results showed that metformin and DCA effectively induced apoptosis in liver cancer cells. A combination treatment of metformin and DCA did not affect viability of primary normal hepatocytes. Metformin upregulated glycolysis in liver cancer cells, thereby increasing sensitivity to the DCA treatment. Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1. In addition, metformin and DCA increased reactive oxygen species levels in liver cancer cells, which induced apoptosis. A combination treatment of metformin and DCA significantly suppressed the tumor growth of liver cancer cells using in vivo xenograft model. Taken together, the combined treatment of metformin and DCA suppressed the growth of liver cancer cells. This strategy may be effective for patients with advanced liver cancer.

Clinical Effect of Systemic Steroids in Patients with Cirrhosis and Septic Shock.

PURPOSE: Evidence regarding the utility of systemic steroids in treating patients with cirrhosis and septic shock remains equivocal. This study aimed to evaluate and elucidate the association of steroid use with outcomes and adverse effects in a cohort of patients with cirrhosis and septic shock. PATIENTS AND METHODS: Retrospective cohort study of patients with cirrhosis and septic shock admitted to a tertiary hospital intensive care unit (ICU) from January 2007 to May 2017, using a validated ICU Datamart. Patients who received vasopressors within 6 h of ICU admission were included in the multivariate analysis. The effect of steroids on outcomes was evaluated using multivariable regression, adjusting for confounding variables. RESULTS: Out of 179 admissions of patients with cirrhosis and septic shock, 56 received steroids during the ICU admission. Patients who received steroids received a higher total dose of vasopressors (91.2 mg vs. 39.1 mg, P = 0.04) and had a lower initial lactate level (1.8 mmol/L vs. 2.6 mmol/L, P = 0.007). The multivariate analysis included 117 patients and showed no significant differences in mortality, length of ICU admission, or length of hospital stay. Bleeding events, delirium, and renal-replacement therapy requirements were also not associated with the use of steroids. CONCLUSION: The use of systemic steroids was more prevalent in cirrhotic patients with higher vasopressor requirements. It was not associated with decreased mortality or increased ICU- and hospital-free days, or to adverse effects.

The longitudinal outcomes of applying non-selective beta-blockers in portal hypertension: real-world multicenter study.

BACKGROUND/AIM: We investigated the effect of non-selective ß-blockers (NSBB) in real-world situations and whether low-dose NSBB is beneficial compared to maximally tolerated doses. METHODS: We performed a retrospective study of 740 patients with cirrhosis requiring prophylactic treatment of esophageal varices: 473 primary prophylaxis (PP: NSBB = 349, non-NSBB = 124) and 267 secondary prophylaxis (SP: NSBB = 200, non-NSBB = 67). The NSBB group was divided into low-dose (≤ 80 mg/day) and high-dose (> 80 mg/day). RESULTS: In the PP group, NSBB treatment reduced mortality and showed the most pronounced effect in patients with moderate/severe ascites (hazard ratio [HR], 0.46; p < 0.01), HVPG ≥ 16 mmHg (HR, 0.53; p = 0.04), or CTP class B/C (HR, 0.46; p < 0.01) but not in those with no/mild ascites, HVPG < 16 mmHg, or CTP class A. Low-dose NSBB group showed a significant reduction in mortality compared with non-NSBB (moderate/severe ascites: HR, 0.61; p = 0.02 and CTP class B/C: HR, 0.41; p < 0.01) and the effect size was stronger than the high-dose NSBB. NSBB was associated with a reduced risk of infection (HR, 0.36; p = 0.01). In the SP group, NSBB prolonged survival in patients with moderate/severe ascites (HR, 0.56; p = 0.02), HVPG ≥ 16 mmHg (HR, 0.42; p < 0.01), or CTP class B/C (HR, 0.52; p < 0.01). Low-dose NSBB was more beneficial with 56% risk reduction (p < 0.01) of mortality compared with 33% risk reduction in the high-dose NSBB (p = 0.05). CONCLUSION: NSBB therapy was associated with longer survival in PP and SP groups who had an advanced stage of cirrhosis. Moreover, low-dose NSBB exhibited a better benefit than a standard-titrated high-dose NSBB with better tolerability.

Environmental risk factors and comorbidities of primary biliary cholangitis in Korea: a case-control study.

BACKGROUND/AIMS: The risk factors for the development of primary biliary cholangitis (PBC) is unclear. This study aimed to investigate the risk factors associated with PBC in Korea through a questionnaire survey. METHODS: Consecutively enrolled 103 PBC patients from six referral hospitals and 100 age- and sex-matched community controls participated in this study. A standardized questionnaire survey including demographics, lifestyle, individual and familial medical history and reproductive history was prospectively collected and analyzed. RESULTS: The PBC patients had a mean age of 58.3 years and a female proportion of 86.4%. The age- and sex-matched controls had a similar educational level and economic status to the PBC patients. Among the lifestyle factors, the multivariable analysis showed smoking including both first-hand and second-hand (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.06 to 3.93), history of autoimmune diseases (OR, 2.46; 95% CI, 1.06 to 6.35), and family history of PBC (OR, 17.76; 95% CI, 1.77 to 2,418.74) were significantly associated with PBC, whereas alcohol intake was negatively associated with PBC. Among reproductive factors, the number of induced abortions was significantly associated with PBC, while the number of full-term deliveries was negatively associated with PBC. CONCLUSION: A family history of PBC, accompanying autoimmune diseases, and smoking were significantly associated with PBC. More induced abortions and less full-term deliveries were associated with PBC in women. In contrast, mild to moderate alcohol intake was negatively associated with PBC. Further studies are warranted to validate the results of this study and to search for clues about the pathogenesis of PBC.

Empirical Treatment With Carbapenem vs Third-generation Cephalosporin for Treatment of Spontaneous Bacterial Peritonitis.

BACKGROUND & AIMS: Third-generation cephalosporins (TGCs) are recommended as first-line antibiotics for treatment of spontaneous bacterial peritonitis (SBP). However, antibiotics against multidrug-resistant organisms (such as carbapenems) might be necessary. We aimed to evaluate whether carbapenems are superior to TGC for treatment of SBP. METHODS: We performed a retrospective study of 865 consecutive patients with a first presentation of SBP (275 culture positive; 103 with TGC-resistant bacterial infections) treated at 7 referral centers in Korea, from September 2013 through January 2018. The primary outcome was in-hospital mortality. We made all comparisons using data from patients whose baseline characteristics were balanced by inverse probability of treatment weighting. RESULTS: Of patients who initially received empirical treatment with antibiotics, 95 (11.0%) received carbapenems and 655 (75.7%) received TGCs. Among the entire study cohort, there was no significant difference in in-hospital mortality between the carbapenem (25.8%) and TGC (25.3%) groups (adjusted odds ratio [aOR], 0.97; 95% CI, 0.85-1.11; P = .66). In the subgroup of patients with high chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores (score of 7 or greater, n = 314), carbapenem treatment was associated with lower in-hospital mortality (23.1%) than in the TGC group (38.8%) (aOR, 0.84; 95% CI, 0.75-0.94; P=.002). In contrast, among patients with lower CLIF-SOFA scores (n = 436), in-hospital mortality did not differ significantly between the carbapenem group (24.7%) and the TGC group (16.0%) (aOR, 1.06; 95% CI, 0.85-1.32; P = .58). CONCLUSIONS: For patients with a first presentation of SBP, empirical treatment with carbapenem does not reduce in-hospital mortality compared to treatment with TGCs. However, among critically ill patients (CLIF-SOFA scores ≥7), empirical carbapenem treatment was significantly associated with lower in-hospital mortality than TGCs.

Individualized surveillance of chronic hepatitis B patients according to hepatocellular carcinoma risk based on PAGE-B scores.

BACKGROUND AND AIMS: Current guidelines for chronic hepatitis B (CHB) patients are to undergo surveillance for hepatocellular carcinoma (HCC) with 6-month ultrasonography. We aimed to compare detection rates of very-early-stage HCC in two groups: group A, undergoing 6-month ultrasonography versus group B, undergoing 6-month ultrasonography alternating with dynamic computed tomography (CT). METHODS: This retrospective study assessed 2151 CHB patients under entecavir/tenofovir therapy from 2007 to 2016. Detection rates of very-early-stage HCC were compared between groups A/B at intermediate/high risk based on platelets, age, gender-hepatitis B scores. The primary endpoint was the proportion of patients in each group with very-early-stage HCC. Cox proportional hazards model was used to assess the effect of surveillance modalities to detect very-early-stage HCC. RESULTS: Five-year cumulative HCC incidence rates in group A were 15.0% not significantly different from 18.2% in group B at high risk (P = 0.17). Detection rates of very-early-stage HCC were significantly higher in group B than in group A (P < 0.001), and surveillance using CT alternating with ultrasonography was significantly associated with detection of very-early-stage HCC (hazard ratio 3.89, P < 0.001). Among intermediate-risk patients, difference between detection rates of very-early-stage HCC in groups A and B was not significant (P = 0.30), and surveillance using CT alternating with ultrasonography was not significantly associated with detection of very-early-stage HCC (hazard ratio 1.61, P = 0.23). CONCLUSION: In high-risk CHB patients, surveillance using CT alternating with ultrasonography led to higher detection rates of very-early-stage HCC compared to surveillance using ultrasonography.

A Cohort Study Examining the Interaction of Alcohol Consumption and Obesity in Hepatic Steatosis and Mortality.

OBJECTIVE: To study the interaction of alcohol consumption with body mass index (BMI) in the development of hepatic steatosis and mortality. PARTICIPANTS AND METHODS: We conducted a retrospective cohort study of 18,506 participants without fatty liver disease or cirrhosis at enrollment in the Mayo Clinic Biobank from April 9, 2009, through March 31, 2016. Participants were classified by self-reported alcohol consumption status (nondrinkers, moderate drinkers [0 to 2 drinks per day], and heavy drinkers [>2 drinks per day]). The primary outcome of interest was the incidence of hepatic steatosis, identified by International Classification of Diseases, Ninth Revision code and confirmed with imaging. The secondary outcome of interest was all-cause mortality. Multivariate Cox regression analysis determined the impact of alcohol consumption stratified by BMI on outcomes compared with nondrinkers. RESULTS: The cohort (mean ± SD age, 55.8±16.9 years; 63.8% female; mean ± SD BMI, 28.8±6.1 kg/m2) of 18,506 participants included 3657 (19.8%) nondrinkers, 14,236 (76.9%) moderate drinkers, and 613 (3.3%) heavy drinkers at enrollment. After a median follow-up of 5.8 years (interquartile range, 3.8 to 7.2 years), 684 participants had development of hepatic steatosis and 968 died. In moderate drinkers, the risk of hepatic steatosis development was high in the obese group (adjusted hazard ratio [AHR], 1.31; 95% CI, 1.03 to 1.67), insignificant in the overweight group (AHR, 0.86; 95% CI, 0.58 to 1.26), and decreased in the normal-BMI group (AHR, 0.48; 95% CI, 0.26 to 0.90). Heavy drinkers had an increased risk of hepatic steatosis irrespective of BMI. Moderate alcohol use was associated with decreased mortality in the normal-weight (AHR, 0.44; 95% CI, 0.34 to 0.58) and overweight (AHR, 0.70; 95% CI, 0.56 to 0.88) groups but not in the obese group (AHR, 0.80; 95% CI, 0.64 to 1.00). CONCLUSION: In obese individuals, even moderate alcohol use is associated with the development of hepatic steatosis. Moderate alcohol consumption is associated with lower mortality in normal-BMI and overweight individuals but not in those who are obese.

Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study.

Background and Aim: Previous studies reported that serum myostatin is associated with sarcopenia. We aimed to elucidate the association between serum myostatin levels and hepatocellular carcinoma (HCC) development in patients with alcoholic liver cirrhosis (ALC). Methods: This retrospective, multicenter study assessed 1077 Asian ALC patients enrolled from 2007 to 2017. The primary endpoint was the development of HCC within 5 years. Cox proportional hazards model analyses were used to assess the association of serum myostatin levels and HCC development. The time-dependent areas under the receiver operating characteristic curve (AUROC) of serum myostatin for 5-year HCC development were calculated. Serum myostatin levels were measured using an enzyme-linked immunosorbent assay with samples collected on the index date. Results: During a median follow-up of 2.5 years, 5-year cumulative HCC incidence rates were 6.7% in the total population. The median level of serum myostatin was 3.3 ng/mL (interquartile, 2.1-5.2 ng/mL). The AUROC of serum myostatin for 5-year HCC development was 0.78 (95% confidence interval [CI], 0.76-0.81). In Cox proportional hazards model analyses, age, gender, platelet counts, and serum myostatin levels were independent risk factors for HCC development (adjusted hazard ratios [HRs] of age, male gender, platelet counts, and serum myostatin: 1.03, 2.79, 0.996, 1.18, respectively; all p < 0.05). Patients with high myostatin levels had a significantly higher risk of 5-year HCC development than those with low myostatin levels (HR 7.53, p < 0.001). Conclusion: Higher serum myostatin levels were significantly associated with a higher risk of developing HCC in ALC patients, which could identify high-risk patients who need stringent surveillance.