Tooth caries classification with quantitative light-induced fluorescence (QLF) images using convolutional neural network for permanent teeth in vivo.

BACKGROUND: Owing to the remarkable advancements of artificial intelligence (AI) applications, AI-based detection of dental caries is continuously improving. We evaluated the efficacy of the detection of dental caries with quantitative light-induced fluorescence (QLF) images using a convolutional neural network (CNN) model. METHODS: Overall, 2814 QLF intraoral images were obtained from 606 participants at a dental clinic using Qraypen C® (QC, AIOBIO, Seoul, Republic of Korea) from October 2020 to October 2022. These images included all the types of permanent teeth of which surfaces were smooth or occlusal. Dataset were randomly assigned to the training (56.0%), validation (14.0%), and test (30.0%) subsets of the dataset for caries classification. Moreover, masked images for teeth area were manually prepared to evaluate the segmentation efficacy. To compare diagnostic performance for caries classification according to the types of teeth, the dataset was further classified into the premolar (1,143 images) and molar (1,441 images) groups. As the CNN model, Xception was applied. RESULTS: Using the original QLF images, the performance of the classification algorithm was relatively good showing 83.2% of accuracy, 85.6% of precision, and 86.9% of sensitivity. After applying the segmentation process for the tooth area, all the performance indics including 85.6% of accuracy, 88.9% of precision, and 86.9% of sensitivity were improved. However, the performance indices of each type of teeth (both premolar and molar) were similar to those for all teeth. CONCLUSION: The application of AI to QLF images for caries classification demonstrated a good performance regardless of teeth type among posterior teeth. Additionally, tooth area segmentation through background elimination from QLF images exhibited a better performance.

Association between periodontal disease and hypertriglyceridemia: Propensity score matching analysis using the 7th Korea National Health and Nutrition Examination Survey.

The prevalence of periodontitis and dyslipidemia continues to increase, and several studies have reported an association between the 2. Therefore, we assessed the relationship between periodontitis and hypertriglyceridemia using propensity score matching to efficiently address confounding factors, as well as complex sample analysis with data from Korea National Health and Nutrition Examination Survey VII (2016-2018). To match the 1:1 ratio between the groups with and without periodontitis, the propensity scores of covariates, such as age, sex, education, income, smoking, drinking, obesity, and diabetes mellitus, were calculated using logistic regression. Both results of logistic regression analysis using complex sample design for whole and matched sample after propensity score matching demonstrated a significant association between hypertriglyceridemia and periodontitis, of which the adjusted odds ratio was 1.28 (95% confidence interval = 1.10-1.50) and 1.29 (95% confidence interval = 1.09-1.52), respectively. Our findings suggest that dental healthcare workers can help raise awareness among patients with periodontitis regarding the association between periodontitis and hypertriglyceridemia, which may help them manage the condition and receive treatment.

Efficacy and safety of sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir for hepatitis C in Korea: a Phase 3b study.

BACKGROUND/AIMS: Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir for 12 weeks in HCV-infected Korean adults. METHODS: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir-velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. RESULTS: Of 53 participants receiving sofosbuvir-velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir-velpatasvir-voxilaprevir achieved SVR 12. Overall, sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. CONCLUSION: Treatment with sofosbuvir-velpatasvir or sofosbuvir-velpatasvir-voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

Clinical Outcomes and Validation of Ursodeoxycholic Acid Response Scores in Patients with Korean Primary Biliary Cholangitis: A Multicenter Cohort Study.

Background/Aims: The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted. Methods: A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated. Results: After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCA response rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS <1.41 (n=97). The area under the receiver operating characteristic curve of URS in predicting UDCA response was 0.84 (95% confidence interval, 0.78 to 0.88). During a median follow-up of 6.5 years, liver-related events developed in 18 patients (10.4%). Among 117 patients with PBC stage I-III by histological evaluation, the 5-year liver-related event-free survival rate differed according to the URS; 100% for URS ≥1.41 and 86.5% for URS <1.41 (p=0.005). Conclusions: URS demonstrated good performance in predicting a UDCA treatment response in Asian PBC patients. In addition, the risk of liver-related events differed according to the URS for the PBC stage. Thus, URS can be used to predict the response and clinical outcome in patients with PBC.

The Clinical Courses and Prognosis of Cirrhotic Patients after First Acute Decompensation: Prospective Cohort Study.

BACKGROUND: The European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium suggested that the clinical courses after acute decompensation (AD) stratify the long-term prognosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre acute-on-chronic liver failure (pre ACLF), and ACLF. However, previous studies included patients with a history of previous AD and had limitations associated with identifying the clinical factors related to prognosis after the first AD. METHOD: The prospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort included cirrhotic patients who were hospitalised with first AD between July 2015 and August 2018. We analysed the factors associated with readmission after the first AD and compared the characteristics and prognosis among each subgroup to evaluate the risk factors for the occurrence of pre ACLF after AD. RESULT: A total of 746 cirrhotic patients who were hospitalised with first AD were enrolled. The subgroups consisted of SDC (n = 565), UDC (n = 29), pre ACLF (n = 28), and ACLF (n = 124). Of note, pre ACLF showed a poorer prognosis than ACLF. The risk factors associated with readmission within 3 months of first AD were non-variceal gastrointestinal (GI) bleeding, hepatic encephalopathy (HE), and high MELD score. Viral aetiology was associated with the occurrence of pre ACLF compared with alcohol aetiology regardless of baseline liver function status. CONCLUSION: Cirrhotic patients with first AD who present as non-variceal GI bleeding and HE can easily relapse. Interestingly, the occurrence of AD with organ failure within 3 months of first AD (pre ACLF) has worse prognosis compared with the occurrence of organ failure at first AD (ACLF). In particular, cirrhotic patients with viral hepatitis with/without alcohol consumption showed poor prognosis compared to other aetiologies. Therefore, patients with ACLF after AD within 3 months should be treated more carefully and definitive treatment through LT should be considered.

Risk of liver fibrosis in patients with prediabetes and diabetes mellitus.

The aim of this study was to assess the risk of liver fibrosis in those with no glucose intolerance, prediabetes, or diabetes. A cross-sectional study was conducted based on a cohort from a health examination program which included a magnetic resonance elastography (MRE). Participants were classified into three groups according to glucose tolerance: no glucose intolerance, prediabetes, and diabetes mellitus. Liver fibrosis was evaluated by liver stiffness measurement (LSM) value using two-dimensional real-time MRE. The risk of significant liver fibrosis was compared among three groups. A total of 2,090 subjects were included: no glucose intolerance (n = 889); prediabetes (n = 985); and diabetes (n = 216). Mean values of LSM in those with no glucose intolerance, prediabetes, and diabetes were 2.37 ± 0.43 kPa, 2.41 ± 0.34 kPa, and 2.65 ± 0.70 kPa, respectively (p<0.001). Proportions of significant fibrosis (LSM ≥2.97 kPa) in no glucose intolerance, prediabetes, and diabetes groups were 3.1%, 4.4%, and 16.7%, respectively (p<0.001). Compared with those with no glucose intolerance, those with diabetes had higher risk of significant fibrosis (adjusted odds ratio [aOR]: 3.02, 95% confidence interval [CI]: 1.57-5.81, p<0.001). However, there was no difference between prediabetes and no glucose intolerance (aOR: 1.05, 95% CI: 0.59-1.86, p = 0.876). A subgroup analysis also showed that prediabetes, unlike diabetes, was not associated with significant fibrosis in subjects with or without liver disease. Diabetes, but not prediabetes, is a risk factor for significant liver fibrosis. This finding is consistent regarldess of the pressence of liver disease.

Platelet-to-White Blood Cell Ratio Is Associated with Adverse Outcomes in Cirrhotic Patients with Acute Deterioration.

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9−15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

ω-3 fatty acid-enriched parenteral nutrition shortens hospital stay in acute variceal bleeding cirrhotic patients.

ABSTRACT: Acute variceal bleeding, a crucial complication of liver cirrhosis requires high energy expenditures but gastrointestinal bleeding limits enteral feeding in the acute stage. We investigated the safety and efficacy of ω-3 fatty acid-enriched parenteral nutrition in acute variceal bleeding patients.In this retrospective study, a total of 208 cirrhotic patients with acute variceal bleeding who underwent parenteral nutrition in the absence of enteral nutrition were enrolled. Among the patients, 86 patients received ω-3 fatty-acid-enriched parenteral nutrition. The primary endpoint was to evaluate the duration of hospital stay and the presence of clinical complications of liver cirrhosis.The mean age of the patients enrolled was 54.9 years-old and 185 patients (88.9%) were male. The cause of liver cirrhosis, Child-Pugh score and comorbidities were statistically not different. Patients with ω-3 enriched parenteral nutrition had a significantly lower systolic blood pressure and total bilirubin levels. The difference in the in-hospital mortality (P = .813) or rate of complications (P = .880) was not statistically significant. The duration of hospital stay was significantly shorter in the patients who underwent ω-3 fatty acid-enriched parenteral nutrition (10.7 ±â€Š7.3 vs 7.9 ±â€Š4.2 days, P = .001).In liver cirrhosis patients with acute variceal bleeding, ω-3 fatty acid-enriched parenteral nutrition significantly decreased the length of hospital stay. Further prospective studies to consolidate these findings are warranted.

Mitochondrial Targeting Domain Homologs Induce Necrotic Cell Death Via Mitochondrial and Endoplasmic Reticulum Disruption.

The mitochondrial targeting domain (MTD) of Noxa contributes to its mitochondrial localization and to apoptosis induction. As a peptide, MTD fused with octa-arginine (R8), a CPP, induces necrosis related to intracellular calcium influx and destruction of mitochondria and endoplasmic reticulum. We searched for homologs of MTD, and compared their cell killing capability when fused with R8. Three of the seven peptides triggered cell death with similar mechanisms. The comparative analysis of peptide sequences showed that four amino acid sites of MTD are critical in regulating necrosis, suggesting the potential to generate artificial, adjustable cytotoxic peptides, which could be effective medicines for many diseases. Thus, homologs functionality could hint to the functions of their belonging proteins.

Distinctive HBV Replication Capacity and Susceptibility to Tenofovir Induced by a Polymerase Point Mutation in Hepatoma Cell Lines and Primary Human Hepatocytes.

Tenofovir disoproxil fumarate (TDF) has been regarded as the most potent drug for treating patients with chronic hepatitis B (CHB). However recently, viral mutations associated with tenofovir have been reported. Here, we found a CHB patient with suboptimal response after more than 4 years of TDF treatment. Clonal analysis of hepatitis B virus (HBV) isolated from sequential sera of this patient identified the seven previously reported TDF-resistant mutations (CYELMVI). Interestingly, a threonine to alanine mutation at the 301 amino acid position of the reverse-transcriptase (RT) domain, (rtT301A), was commonly accompanied with CYELMVI at a high rate (72.7%). Since the rtT301A mutation has not been reported yet, we investigated the role of this naturally occurring mutation on the viral replication and susceptibility to tenofovir in various liver cells (hepatoma cells as well as primary human hepatocytes). A cell-based phenotypic assay revealed that the rtT301A mutation dramatically impaired the replication ability with meaningful reduction in sensitivity to tenofovir in hepatoma cell lines. However, attenuated viral replication by the rtT301A mutation was significantly restored in primary human hepatocytes (PHHs). Our findings suggest that the replication capability and drug sensitivity of HBV is different between hepatoma cell lines and PHHs. Therefore, our study emphasizes that validation studies should be performed not only in the liver cancer cell lines but also in the PHHs to understand the exact viral fitness under antiviral pressure in patients.

Hepatocellular Carcinoma in Korea: an Analysis of the 2015 Korean Nationwide Cancer Registry.

Background/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death in Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2015. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative sample of patients newly diagnosed with HCC in Korea, were analyzed. A total of 1,558 patients with HCC registered in the KPLCR in 2015 were investigated. Results: The median age was 61.0 years (interquartile range, 54.0-70.0 years), and men accounted for 79.7% of the subjects. Hepatitis B virus infection was the most common underlying liver disease (58.1%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stage 0, A, B, C, and D HCCs accounted for 14.2%, 31.5%, 7.6%, 39.0%, and 7.8% of patients, respectively. Transarterial therapy (32.1%) was the most commonly performed initial treatment, followed by surgical resection (23.2%), best supportive care (20.2%), and local ablation therapy (10.7%). Overall, 34.5% of patients were treated in accordance with the BCLC guidelines: 59.2% in stage 0/A, 48.4% in stage B, 18.1% in stage C, and 71.6% in stage D. The 1-, 3-, and 5-year OS rates were 67.1%, 50.9%, and 27.0%, respectively. Conclusions: In 2015, approximately 45% of Korean HCC cases were diagnosed at a very early or early stage, and 35% of patients underwent potentially curative initial treatment. BCLC guidance was followed in 34.5% of patients; in patients with stage B or C disease, there was relatively low adherence.

Pleural Effusion after Hepatic Radiofrequency Ablation with Artificial Ascites: Clinical Spectrum and Significance.

PURPOSE: To retrospectively investigate incidence, clinical outcome, and risk factors of iatrogenic pleural effusion in patients with hepatic tumors undergoing radiofrequency (RF) ablation using artificial ascites (AA). MATERIALS AND METHODS: Patients (N = 163) who underwent RF ablation using AA were classified into pleural effusion and non-pleural effusion groups according to the presence of pleural effusion on immediate follow-up CT and chest radiograph after RF ablation. The pleural effusion group included asymptomatic and symptomatic subgroups. The incidence and subsequent clinical outcomes of patients developing pleural effusion after RF ablation were evaluated. RESULTS: Overall, 96 patients (58.9%) developed pleural effusion, which resolved in 4.4 d ± 3.1. Hospital length of stay in the pleural effusion group was longer than the non-pleural effusion group (6.5 d ± 2.6 vs 5.7 d ± 2.8, P < .01). The pleural effusion group had longer AA infusion time (P = .01), larger infused AA volume (P < .01), and longer ablation time (P < .01) than the non-pleural effusion group. Eighteen patients (18.8%) developed symptomatic pleural effusion and had a larger infused AA volume than asymptomatic patients with pleural effusion (P < .01). Pleural effusion duration and hospital length stay were also longer in the symptomatic pleural effusion subgroup than in the asymptomatic subgroup (P < .01). Infused AA volume was the only independent prognostic factor of pleural effusion duration in multivariate analysis (P = .038). CONCLUSIONS: Pleural effusion frequently occurs after RF ablation using AA. Although generally considered negligible, pleural effusion could be a clinical problem and prolong hospitalization. Therefore, operators should be careful not to infuse too much AA when performing RF ablation.

Long-term hepatitis B surface antigen (HBsAg) kinetics during entecavir treatment in Korean patients-Functional cure unlikely.

The aim of this study was to investigate the on-treatment kinetics of quantitative HBsAg during entecavir therapy to predict the treatment period needed to achieve functional cure. From a cohort of 1009 CHB treatment-naïve patients who were started on entecavir, the kinetics of quantitative HBsAg decline was assessed in 410 patients by a linear mixed model. The difference in the kinetics of quantitative HBsAg was determined based on the HBeAg positivity, HBeAg seroclearance and presence of baseline liver cirrhosis. Among the 410 patients, 213 patients (52.0%) were HBeAg-positive and 217 patients (66.1%) were male with a median age of 48 years. During a median follow-up of 53.5 months, the quantitative HBsAg level showed a slow but consistent decrease. The expected log qHBsAg levels as a function of time during entecavir treatment in HBeAg(+) and HBeAg(-) patients were 3.4773-0.0039 × Months and 3.1853-0.0036 × Months, respectively. The estimated time to clearance of quantitative HBsAg in our study was greater than 74.1 years in HBeAg-positive patients and 73.5 years in HBeAg-negative patients. The calculated time to achieve functional cure is lifelong without regard to HBeAg seroclearance or presence of liver cirrhosis. The mathematical modelling from a long-term follow-up of chronic hepatitis B patients on entecavir shows that HBsAg clearance requires decades of treatment. Thus, lifelong therapy is inevitable in entecavir-treated patients to achieve functional cure.

Risk of metabolic syndrome in participants within the normal range of alanine aminotransferase: A population-based nationwide study.

This study aimed to investigate the risk of metabolic syndrome (MS) in participants whose alanine aminotransferase (ALT) levels were within the normal range in the general population. A cross-sectional study was conducted using nationally representative samples from the Korea National Health and Nutrition Examination Survey 2007-2015. A total of 43,402 adults (men, 17,535; women, 25,867) with ALT ≤40 U/L without a history of hepatitis B and C, liver cirrhosis, or liver cancer were analyzed. The risk of MS was evaluated according to the ALT level. The prevalence of MS significantly increased as the ALT levels increased. The proportions of MS in men were 12.6%, 25.2%, and 39.7% in the ALT levels of <15, 15~30, and 30~40 U/L, respectively (p < 0.001), and those of women were 7.2%, 23.3%, and 44.7% in the ALT levels of <10, 10~20, and 20~40 U/L, respectively (p < 0.001). There was an ALT-dependent relationship in the risk of MS in participants with normal ALT level after adjustment for age, alcohol intake, and body mass index. The adjusted odds ratio (aOR) of MS in men was 2.48 (95% confidence interval [CI], 2.16-2.85) in an ALT level of 30~40 U/L compared with that in ALT <15 U/L (p < 0.001), and the aOR of MS in women was 2.67 (95% CI, 2.26-3.15) in an ALT level of 20~40 U/L compared with that in ALT <10 U/L (p < 0.001). Although within the normal range of ALT, the risk of MS increases as the ALT levels increase. The ALT level in the general population without a history of chronic liver disease may be a useful marker to evaluate for MS.

Use of cyclooxygenase inhibitor and the risk of hepatocellular carcinoma in patients with chronic hepatitis B: A nested case-control study using a nationwide population-based data.

The study aimed to investigate the relationship between the use of COX inhibitors and the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB) using a nationwide population-based data. A nested case-control study was conducted using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) from 2002 to 2013 in Korea. We compared the use of COX inhibitors between HCC cases and matched controls by categorizing 5 groups according to the cumulative defined daily dose (cDDD, <28, 28-90, 91-180, 181-360, and >360) adjusting the use of antiviral agents. A total of 4980 patients with CHB were analysed as 996 HCC cases and 3984 matched controls. The number of COX inhibitor users (≥28 cDDD) was 358 patients (36%) and 1814 patients (45%) in the HCC group and control group, respectively. The use of COX inhibitors was significantly associated with a decreased risk of HCC development compared with nonusers (adjusted odds ratio [OR] 0.62, 95% confidence interval [CI] 0.52-0.73, P < .001). There was a dose-dependent inverse relationship between the use of COX inhibitors and the risk of HCC. The adjusted ORs were 0.75 (95% CI: 0.63-0.90), 0.41 (95% CI: 0.31-0.56), 0.38 (95% CI: 0.25-0.57) and 0.49 (95% CI: 0.31-0.79) for the 28-90, 91-180, 181-360 and >360 cDDDs, respectively (P < .01). In conclusion, the use of COX inhibitors was associated with a reduced risk of HCC in CHB. COX inhibitor may have a chemopreventive role in HCC development in patients with chronic liver disease.