Background: We assessed the myocardial infarction (MI), stroke, and all-cause death risks during follow-up according to the low-density lipoprotein cholesterol (LDL-C) levels among older adults. Methods: The Korean National Health Insurance Service datasets (2002 to 2020) were used for this population-based cohort study. The hazards of MI, stroke, and all-cause mortality during follow-up were analyzed according to LDL-C level in individuals aged ≥65 years without baseline cardiovascular diseases (n=1,391,616). Results: During a mean 7.55 years, 52,753 MIs developed; 84,224 strokes occurred over a mean 7.47 years. After a mean 8.50 years, 233,963 died. A decrease in LDL-C was associated with lower hazards of MI and stroke. The decreased hazard of stroke in lower LDL-C was more pronounced in statin users, and individuals with diabetes or obesity. The hazard of all-cause death during follow-up showed an inverted J-shaped pattern according to the LDL-C levels. However, the paradoxically increased hazard of mortality during follow-up in lower LDL-C was attenuated in statin users and individuals with diabetes, hypertension, or obesity. In statin users, lower LDL-C was associated with a decreased hazard of mortality during follow-up. Conclusion Among the elderly, lower LDL-C was associated with decreased risks of MI and stroke. Lower LDL-C achieved by statins in the elderly was associated with a decreased risk of all-cause death during follow-up, suggesting that LDL-C paradox for the premature death risk in the elderly should not be applied to statin users. Intensive statin therapy should not be hesitated for older adults with cardiovascular risk factors including diabetes.

Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Background and Objectives: Autologous or allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) have been applied in clinical trials to treat liver disease. However, only a few studies are comparing the characteristics of autologous MSCs from patients and allogeneic MSCs from normal subjects. Methods: and Results: We compared the characteristics of BMSCs (BCs and BPs, respectively) isolated from six healthy volunteers and six patients with cirrhosis. In passage 3 (P3), senescent population and expression of p53 and p21 were slightly higher in BPs, but the average population doubling time for P3–P5 in BPs was approximately 65.3±11.1 h, which is 18.4 h shorter than that in BCs (83.7±9.2 h). No difference was observed in the expression of CD73, CD90, or CD105 between BCs and BPs. Adipogenic differentiation slightly increased in BCs, but the expression levels of leptin, peroxisome proliferator-activated receptor γ, and CCAAT-enhancer-binding protein α did not vary between differentiated BCs and BPs. While ATP and reactive oxygen species levels were slightly lower in BPs, mitochondrial membrane potential, oxygen consumption rate, and expression of mitochondria-related genes such as cytochrome c oxidase 1 were not significantly different between BCs and BPs. Conclusions Taken together, there are marginal differences in the proliferation, differentiation, and mitochondrial activities of BCs and BPs, but both BMSCs from patients with cirrhosis and healthy volunteers show comparable characteristics.

BACKGROUND/AIMS: Acute hepatic dysfunction combined with alcoholic hepatitis (AH) in alcoholic cirrhosis is related to hepatic hypo-perfusion secondary to intrahepatic necroinflammation, neoangiogenesis, and shunt. The hepatic vein arrival time (HVAT) assessed by microbubble contrast-enhanced ultrasonography (CEUS) is closely correlated with the severity of intrahepatic changes. We investigated the usefulness of HVAT to predict short-term mortality of AH in cirrhosis. METHODS: Thirty-nine patients with alcoholic cirrhosis (27 males) and AH were prospectively enrolled. HVAT study was performed within 3 days after admission using ultrasonic contrast (SonoVue®). The primary outcome was 12-week mortality. RESULTS: Twelve-week mortality developed in nine patients. HVAT was significantly different between the mortality and survival groups (9.3±2.0 seconds vs 12.6±3.5 seconds, p=0.002). The odds ratio of a shortened HVAT for 12-week mortality was 1.481 (95% confidence interval, 1.050–2.090; p=0.025). The area under the receiver operating characteristic curve of HVAT for 12-week mortality was 0.787 (p=0.010). The combination of MDF and HVAT ≥11.0 seconds resulted in an 87.5% survival rate even if the MDF score ≥32; however, HVAT < 11.0 seconds was related with mortality despite a MDF score < 32. CONCLUSIONS: HVAT using microbubble CEUS could be a useful additional index to predict short-term mortality in patients with AH and cirrhosis.
Alcoholics* ; Fibrosis* ; Hepatic Veins ; Hepatitis, Alcoholic* ; Humans ; Liver Cirrhosis, Alcoholic ; Microbubbles ; Mortality ; Odds Ratio ; Pilot Projects* ; Prognosis* ; Prospective Studies* ; ROC Curve ; Survival Rate ; Ultrasonics ; Ultrasonography*

OBJECTIVE: Studies have presented conflicting results regarding the accuracy of ultrasonography (US) for diagnosing portal hypertension (PH). We sought to identify evidence in the literature regarding the accuracy of US for assessing PH in patients with liver cirrhosis. MATERIALS AND METHODS: We conducted a systematic review by searching databases, including MEDLINE, EMBASE, and the Cochrane Library, for relevant studies. RESULTS: A total of 14 studies met our inclusion criteria. The US indices were obtained in the portal vein (n = 9), hepatic artery (n = 6), hepatic vein (HV) (n = 4) and other vessels. Using hepatic venous pressure gradient (HVPG) as the reference, the sensitivity (Se) and specificity (Sp) of the portal venous indices were 69-88% and 67-75%, respectively. The correlation coefficients between HVPG and the portal venous indices were approximately 0.296-0.8. No studies assess the Se and Sp of the hepatic arterial indices. The correlation between HVPG and the hepatic arterial indices ranged from 0.01 to 0.83. The Se and Sp of the hepatic venous indices were 75.9-77.8% and 81.8-100%, respectively. In particular, the Se and Sp of HV arrival time for clinically significant PH were 92.7% and 86.7%, respectively. A statistically significant correlation between HVPG and the hepatic venous indices was observed (0.545-0.649). CONCLUSION: Some US indices, such as HV, exhibited an increased accuracy for diagnosing PH. These indices may be useful in clinical practice for the detection of significant PH.
Hepatic Veins/ultrasonography ; Humans ; Hypertension, Portal/*diagnosis/*ultrasonography ; Liver Cirrhosis/*ultrasonography ; Middle Aged ; Portal Pressure ; Portal Vein/ultrasonography ; Prospective Studies ; Sensitivity and Specificity ; Vascular Resistance

BACKGROUND/AIMS: We evaluated whether colonic transit time (CTT) can predict the degree of bowel preparation in patients with chronic constipation undergoing scheduled colonoscopy in order to assist in the development of better bowel preparation strategies for these patients. METHODS: We analyzed the records of 160 patients with chronic constipation from March 2007 to November 2012. We enrolled patients who had undergone a CTT test followed by colonoscopy. We defined patients with a CTT > or =30 hours as the slow transit time (STT) group, and patients with a CTT <30 hours as the normal transit time (NTT) group. Boston Bowel Preparation Scale (BBPS) scores were compared between the STT and NTT groups. RESULTS: Of 160 patients with chronic constipation, 82 (51%) were included in the STT group and 78 (49%) were included in the NTT group. Patients with a BBPS score of <6 were more prevalent in the STT group than in the NTT group (31.7% vs. 10.3%, P=0.001). Multivariate analysis showed that slow CTT was an independent predictor of inadequate bowel preparation (odds ratio, 0.261; 95% confidence interval, 0.107-0.634; P=0.003). The best CTT cut-off value for predicting inadequate bowel preparation in patients with chronic constipation was 37 hours, as determined by receiver operator characteristic (ROC) curve analysis (area under the ROC curve: 0.676, specificity: 0.735, sensitivity: 0.643). CONCLUSIONS: Patients with chronic constipation and a CTT >30 hours were at risk for inadequate bowel preparation. CTT measured prior to colonoscopy could be useful for developing individualized strategies for bowel preparation in patients with slow CTT, as these patients are likely to have inadequate bowel preparation.
Colon* ; Colonoscopy ; Constipation* ; Humans ; Multivariate Analysis ; ROC Curve ; Sensitivity and Specificity

The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.
Acute Disease ; Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Cholestasis/epidemiology/etiology ; Demography ; Hepatitis A/complications/*diagnosis/mortality ; Humans ; Kidney Failure, Chronic/epidemiology/etiology ; Liver Transplantation ; Middle Aged ; Morbidity ; Republic of Korea ; Retrospective Studies ; Tertiary Care Centers ; Young Adult

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.
Adult ; Aged ; Biopterin/*analogs & derivatives/analysis ; *Chromatography, High Pressure Liquid ; Chronic Disease ; Elasticity Imaging Techniques ; Female ; Hepatic Veins/physiology ; Humans ; Hypertension, Portal/complications/*diagnosis/metabolism ; Liver/pathology ; Liver Cirrhosis/ultrasonography ; Liver Diseases/complications/*diagnosis/metabolism ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Portal Pressure ; Regression Analysis ; Severity of Illness Index

BACKGROUND/AIMS: We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis. METHODS: Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4+/-9.5 y, mean+/-SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated. RESULTS: The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS > or =6: LSM > or =17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4. CONCLUSIONS: The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.
Adult ; Area Under Curve ; *Elasticity Imaging Techniques ; Female ; Hepatic Veins/physiopathology ; Humans ; Liver Cirrhosis/pathology/*ultrasonography ; Male ; Middle Aged ; Odds Ratio ; Predictive Value of Tests ; Prospective Studies ; ROC Curve ; Severity of Illness Index ; Spleen/anatomy & histology ; Splenic Vein/physiology