Publications by authors named "Jeong-Ju Yoo"

69 Publications

Nonalcoholic fatty liver disease is associated with the development of obstructive sleep apnea.

Sci Rep 2021 Jun 29;11(1):13473. Epub 2021 Jun 29.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-no, Jongno-gu, Seoul, 03080, Republic of Korea.

Increasing evidence suggests that obstructive sleep apnea (OSA) is a metabolic syndrome-related disease; however, the association between nonalcoholic fatty liver disease (NAFLD) and OSA is not firmly established. In this study, we investigated the relationship between NAFLD and OSA in a general population drawn from a nationwide population-based cohort. Data from the Korean National Health Insurance System between January 2009 and December 2009 were analyzed using Cox proportional hazards model. NAFLD was defined as a fatty liver index (FLI) ≥ 60 in patients without excessive alcohol consumption (who were excluded from the study). Newly diagnosed OSA during follow-up was identified using claims data. Among the 8,116,524 participants, 22.6% had an FLI score of 30-60 and 11.5% had an FLI ≥ 60. During median follow-up of 6.3 years, 45,143 cases of incident OSA occurred. In multivariable analysis, the risk of OSA was significantly higher in the higher FLI groups (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.12-1.18 for FLI 30-60 and aHR 1.21, 95% CI 1.17-1.26 for FLI ≥ 60). These findings were consistent regardless of body mass index and presence of abdominal obesity. In conclusion, a high FLI score may help identify individuals with a high risk of OSA. Understanding the association between NAFLD and OSA may have clinical implications for risk-stratification of individuals with NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-92703-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241839PMC
June 2021

KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease.

Clin Mol Hepatol 2021 Jul 22;27(3):363-401. Epub 2021 Jun 22.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3350/cmh.2021.0178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273632PMC
July 2021

Adverse outcomes after surgeries in patients with liver cirrhosis among Korean population: A population-based study.

PLoS One 2021 14;16(6):e0253165. Epub 2021 Jun 14.

Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Seoul, Korea.

Background: Patients with liver cirrhosis have an increased risk of in-hospital mortality or postoperative complication after surgery. However, large-scale studies on the prognosis of these patients after surgery are lacking. The aim of the study was to investigate the adverse outcomes of patients with liver cirrhosis after surgery over five years.

Methods And Findings: We used the Health Insurance Review and Assessment Service-National Inpatient Samples (HIRA-NIS) between 2012 and 2016. In-hospital mortality and hospital stay were analyzed using the data. Mortality rates according to the surgical department were also analyzed. Of the 1,662,887 patients who underwent surgery, 16,174 (1.0%) patients had cirrhosis. The in-hospital mortality (8.0% vs. 1.0%) and postoperative complications such as respiratory (6.0% vs. 5.3%) or infections (2.8% vs. 2.4%) was significantly higher in patients with cirrhosis than in those without cirrhosis. In addition, the total hospitalization period and use of the intensive care unit were significantly higher in patients with liver cirrhosis. In propensity score matching analysis, liver cirrhosis increased the risk of adverse outcome significantly [adjusted OR (aOR) 1.67, 95% CI 1.56-1.79, P<0.001], especially in-hospital mortality. In liver cirrhosis group, presence of decompensation or varices showed significantly increased postoperative complication or mortality. Adverse outcomes in patients with cirrhosis was the highest in patients who underwent otorhinolaryngology surgery (aOR 1.86), followed by neurosurgery (aOR 1.72), thoracic and cardiovascular surgery (aOR 1.56), and plastic surgery (aOR 1.36).

Conclusion: The adverse outcomes of patients with cirrhosis is significantly high after surgery, despite advances in cirrhosis treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253165PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202950PMC
June 2021

Extremely rare case of necrotizing gastritis in a patient with autoimmune hepatitis: A case report.

World J Clin Cases 2021 May;9(14):3472-3477

Department of Gastroenterology and Hepatology, Soonchunhyang University School of Medicine, Bucheon 14584, South Korea.

Background: Autoimmune hepatitis can cause liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Its treatment option include the use of steroids and/or immune-suppressive agents such as azathioprine. However, these drugs have some side effects. Thus, close follow-up is needed during treatment. Here, we present an extremely rare case of a patient with an autoimmune hepatitis who died from necrotizing gastritis during immunosuppressive treatment.

Case Summary: A 52-year-old female patient was diagnosed with autoimmune hepatitis. We treated this patient with immunosuppressive agents. High-dose steroid treatment was initially started. Then azathioprine treatment was added while steroid was tapering. Five weeks after the start of treatment, she visited the emergency room due to generalized abdominal pain and vomiting. After computed tomography scan, the patient was diagnosed with necrotizing gastritis and the patient progressed to septic shock. Treatment for sepsis was continued in the intensive care unit. However, the patient died at 6 h after admission to the emergency room.

Conclusion: In patients with autoimmune infections undergoing immunosuppressant therapy, rare complications such as necrotizing gastritis may occur, thus requiring clinical attention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v9.i14.3472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107894PMC
May 2021

Association between alcohol consumption status and obesity-related comorbidities in men: data from the 2016 Korean community health survey.

BMC Public Health 2021 04 15;21(1):733. Epub 2021 Apr 15.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, 170 Jomaru-ro, Wonmi-gu, Bucheon, 14584, Republic of Korea.

Background: This study was performed to investigate the association between the amount of alcohol consumption or binge drinking and obesity-related comorbidities in Korean men.

Methods: A total of 103,048 men aged 19 years or older were investigated in the 2016 Korean Community Health Survey. The participants were divided into five groups according to the standard number of alcoholic drinks consumed per week.

Results: Of the total participants, 20.7% were in the high alcohol consumption group, consuming more than 28 drinks per week. After adjustment for clinical factors, high alcohol consumption was significantly associated with higher odds ratios (ORs) of obesity (OR, 1.449; 95% confidence interval [CI], 1.412 to 1.591; P < 0.0001), hypertension (OR, 1.76; 95% CI, 1.636 to 1.894; P < 0.0001), and dyslipidemia (OR, 1.356; 95% CI, 1.247 to 1.474; P < 0.0001). In contrast, mild to moderate alcohol consumption was associated with a lower risk of diabetes (OR, 0.799; 95% CI, 0.726 to 0.88; P = 0.0015) and high alcohol consumption was not associated with a higher risk of diabetes (OR, 0.945; 95% CI, 0.86 to 1.039; P = 0.0662). Among drinkers, except for social drinkers, binge drinking was significantly associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia.

Conclusions: High alcohol consumption was associated with higher risks of obesity, hypertension, and dyslipidemia in Korean men. In contrast, high consumption was not associated with a higher risk of diabetes. In particular, binge drinkers were associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia compared to non-binge drinkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-021-10776-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051125PMC
April 2021

Association between Lipid Profiles and the Incidence of Hepatocellular Carcinoma: A Nationwide Population-Based Study.

Cancers (Basel) 2021 Mar 30;13(7). Epub 2021 Mar 30.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea.

Background And Aims: Altered lipid metabolism has been implicated in the development of hepatocellular carcinoma (HCC). This study investigated the relationships between lipid profiles and HCC development.

Methods: Data were obtained from the Korean National Health Insurance Service from 2009 to 2017. Cox regression analysis was used to examine the hazard ratios of HCC in 8,528,790 individuals who had undergone health check-ups in 2009.

Results: During a median of 7.3 years follow-up, 26,891 incidents of HCCs were identified. The incidence of HCC (per 100,000 person-years) gradually decreased according to the increase in total-cholesterol and LDL-cholesterol; the incidence of HCC was 69.2, 44.0, 33.9, and 25.8 in quartile-1 (Q1), Q2, Q3, and Q4 population of total-cholesterol, and 63.6, 44.5, 37.2, and 28.3 in Q1, Q2, Q3, and Q4 population of LDL-cholesterol, respectively. Compared to Q1 of total-cholesterol, subjects in higher total-cholesterol levels were associated with a lower incidence of HCC (multiple covariates-adjusted hazard ratio (aHR): Q2 0.61; Q3 0.46; Q4 0.36). These associations were consistently observed in stratified subgroup analysis by the presence of liver cirrhosis or viral hepatitis.

Conclusions: Low serum lipid levels were significantly associated with the increased risk of developing HCC. A low lipid profile might be an independent risk factor and preclinical marker for HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13071599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037932PMC
March 2021

Urinary Microbiome Characteristics in Female Patients with Acute Uncomplicated Cystitis and Recurrent Cystitis.

J Clin Med 2021 Mar 5;10(5). Epub 2021 Mar 5.

Department of Urology, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Korea.

Traditionally, the diagnostic mainstay of recurrent urinary tract infection has been urinary culture. However, the causative uropathogen of recurrent cystitis has not been well established. Urine DNA next-generation sequencing (NGS) can provide additional information on these infections. Herein, we compared urine NGS results and urine cultures in patients with acute uncomplicated cystitis (AUC) and recurrent cystitis (RC), and evaluated the difference in microbiome patterns in the NGS results. Patients who underwent urine culture and NGS due to AUC or RC were retrospectively reviewed. All urine samples were collected via a transurethral catheter and studied utilizing a type of NGS called 16S ribosomal RNA gene amplification and sequencing. The sensitivity of urine NGS was significantly higher than that of conventional urine culture (69.0% vs. 16.7%, < 0.05). The detection rate of urine NGS was slightly lower in the RC group than in the AUC group (67.7% vs. 72.7%). Microbiome diversity was significantly higher in the RC group compared to the AUC group ( = 0.007), and the microbiome composition was significantly different between the AUC and RC groups. In the urine NGS results, , and Enterobacteriaceae were found in the AUC group, and , and spp. were detected in the RC group. Urine NGS can significantly increase the diagnostic sensitivity compared to traditional urine culture methods, especially in RC patients. AUC and RC patients had significant differences in bacterial diversity and patterns. Therefore, recurrent cystitis might be approached from a different perspective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10051097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961880PMC
March 2021

Effect of antiviral therapy in patients with low HBV DNA level on transarterial chemoembolization for hepatocellular carcinoma.

J Viral Hepat 2021 Jul 5;28(7):1011-1018. Epub 2021 Apr 5.

Department of Internal Medicine, Soonchunhyang University College of Medicine Cheonan Hospital, Cheonan, South Korea.

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low-level viremia HBV-HCC receiving non-curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low-level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV-HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non-antiviral group). The definition of low-level viremia was an HBV DNA level <2000 IU/ml. Kaplan-Meier curves, log-rank tests and Cox regression analysis were used for statistical analyses. The median follow-up duration was 39 months (1-174 months). Overall survival (OS) did not differ between groups (P = .227). Barcelona Clinic Liver Cancer stage (BCLC), Child-Pugh (CP) class and α-fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P = .022) was a prognostic factor for 2-year survival. On subgroup analysis, antiviral therapy improved short-term survival in patients with BCLC stage 0 and A (P = .037) and CP class A (P = .04). In patients with low-level viremia, antiviral therapy yielded short-term survival benefits, particularly in patients with early-stage HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvh.13508DOI Listing
July 2021

Glucose Variability and Risk of Hepatocellular Carcinoma in Patients with Diabetes: A Nationwide Population-Based Study.

Cancer Epidemiol Biomarkers Prev 2021 May 2;30(5):974-981. Epub 2021 Mar 2.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea (South).

Background: Although diabetes is a well-known risk factor for hepatocellular carcinoma, exactly which metabolic parameters of diabetes are associated with hepatocellular carcinoma remain unexplored. In this study, we investigated the relationship between glucose variability (GV) and hepatocellular carcinoma in patients with diabetes through a nationwide population-based study.

Methods: A population-based cohort study including 674,178 diabetic subjects participating in more than three health examinations within 5 years from the index year (2009 and 2010) were followed until the end of 2017. The coefficient of variation, SD, variability independent of the mean, and average real variability were calculated as GV indices.

Results: During a median follow-up of 6.7 years, there were 5,494 cases of hepatocellular carcinoma. When groups were classified according to glucose level, the highest risk for hepatocellular carcinoma was observed when the basal blood glucose level was 180 mg/dL or greater [adjusted HR (aHR), 1.19; 95% confidence interval (CI), 1.08-1.31]. We observed increasing trends for the relationship between GV and hepatocellular carcinoma in multivariable Cox proportional analyses. The risk of hepatocellular carcinoma increased by 27% (aHR, 1.27; 95% CI, 1.17-1.38) for the highest quartile of GV relative to the lowest quartile. These findings were consistent regardless of the presence of chronic viral hepatitis or cirrhosis, alcohol consumption, or body mass index.

Conclusions: GV was an independent predictor of hepatocellular carcinoma, even after adjusting for confounding factors. There was a linear relationship between increase in GV and prevalence of hepatocellular carcinoma.

Impact: Visit-to-visit GV might be helpful for identifying patients with diabetes at high risk of hepatocellular carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-1654DOI Listing
May 2021

Weight fluctuation and risk of hepatocellular carcinoma: a nationwide population-based 8-million-subject study.

Hepatol Int 2021 Apr 17;15(2):482-492. Epub 2021 Feb 17.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background/aim: The importance of hepatocellular carcinoma (HCC) caused by obesity has been emphasized. Many studies have shown that weight fluctuations as well as high BMI are associated with various adverse outcomes. In this study, we investigated the relationship between weight fluctuation and HCC in general populations drawn from a nationwide population-based cohort.

Method: A population-based cohort study including 8,001,829 subjects participating in more than three health examinations within 5 years from the index year were followed until the end of 2017. The degree of weight fluctuation and incidence of HCC during the period were evaluated.

Results: When we classified groups according to baseline body mass index (BMI) level, the highest risk for HCC was observed in subjects with BMI of 30 or greater (adjusted hazard ratio [aHR] 1.40, 95% confidence interval [CI] 1.27-1.54). Also, increasing trends for the relationship between weight fluctuation and HCC were observed in multivariable Cox proportional analyses. The risk of HCC increased by 16% (aHR 1.16, 95% CI 1.12-1.20) for the highest quartile of weight fluctuation relative to the lowest quartile. These findings were consistent regardless of the baseline BMI or other metabolic factors. However, these effects of weight fluctuation on HCC were not observed in liver cirrhosis or viral hepatitis subgroups.

Conclusion: Weight fluctuation is an independent predictor of HCC. In the absence of liver cirrhosis or chronic hepatitis, the impact of weight fluctuation on HCC is further emphasized. These results suggest maintaining steady weight is recommended to reduce the risk of HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-021-10149-yDOI Listing
April 2021

The cut-off value of transient elastography to the value of hepatic venous pressure gradient in alcoholic cirrhosis.

Clin Mol Hepatol 2021 01 3;27(1):197-206. Epub 2020 Dec 3.

UB Songdo Hospital, Ulaanbaatar, Mongolia.

Background/aims: The hepatic venous pressure gradient (HVPG) reflects portal hypertension, but its measurement is invasive. Transient elastography (TE) is a noninvasive method for evaluating liver stiffness (LS). We investigated the correlation between the value of LS, LS to platelet ratio (LPR), LS-spleen diameter-to-platelet ratio score (LSPS) and HVPG according to the etiology of cirrhosis, especially focused on alcoholic cirrhosis.

Methods: Between January 2008 and March 2017, 556 patients who underwent HVPG and TE were consecutively enrolled. We evaluated LS, LPR, and LSPS according to the etiology of cirrhosis and analyzed their correlations with HVPG.

Results: The LS value was higher in patients with alcoholic cirrhosis than viral cirrhosis based on the HVPG (43.5 vs. 32.0 kPa, P<0.001). There were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups, and the areas under the curves for the LPR and LSPS in subgroups according to HVPG levels were not superior to that for LS. In alcoholic cirrhosis, the LS cutoff value for predicting an HVPG ≥10 mmHg was 32.2 kPa with positive predictive value (PPV) of 94.5% and 36.6 kPa for HVPG ≥12 mmHg with PPV of 91.0%.

Conclusion: The LS cutoff value should be determined separately for patients with alcoholic and viral cirrhosis. In alcoholic cirrhosis, the LS cutoff values were 32.2 and 36.6 kPa for predicting an HVPG ≥10 and ≥12 mmHg, respectively. However, there were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3350/cmh.2020.0171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820198PMC
January 2021

Association between Health Indicators and Health-Related Quality of Life according to Physical Activity of Older Women.

Healthcare (Basel) 2020 Nov 22;8(4). Epub 2020 Nov 22.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14854, Korea.

The purpose of this study was to compare sociodemographic factors, health factors and nutritional status according to the physical activity of older women, and to analyze the factors affecting their quality of life. The subjects of this study were 5661 older women aged 60 or older who participated in the Korean National Health and Nutrition Survey (KNHANES) from 2008 to 2013. The socioeconomic factors, subjective health status and disease status, lifestyle and dietary quality, and life quality were compared among two groups (active group and inactive group). The inactive group had significantly higher rates of obesity and unemployment, comorbidities, numbers without spouses, experiencing stress, poor subjective health status, depression or suicidal thoughts, and also higher rates of skipping meals. The life quality index and dietary quality was also significantly lower in the inactive group, and subjects experienced significantly higher pain or discomfort and problems in mobility and the usual activities. The results of multivariate analysis after adjusting for age in groups engaging in physical activities showed the life quality index to increase in accordance with the diet quality, economic income, and education level. It was confirmed that life quality was significantly low if the participant showed a poor subjective health evaluation, obese with many diseases, spouseless, and experienced high levels of stress. Considering the rapid aging and high life expectancy of women, regular physical activity is very important for maintaining health and improving the life quality of older women, and it is believed that comprehensive attention and management of lifestyle and diet quality are necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/healthcare8040507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712132PMC
November 2020

Application of Hepatic Venous Pressure Gradient to Predict Prognosis in Cirrhotic Patients with a Low Model for End-Stage Liver Disease Score.

Diagnostics (Basel) 2020 Oct 10;10(10). Epub 2020 Oct 10.

Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul 04401, Korea.

Background/aim: We aimed to derive a model representing the dynamic status of cirrhosis and to discriminate patients with poor prognosis even if the Model for End-Stage Liver Disease (MELD) score is low.

Methods: This study retrospectively enrolled 700 cirrhotic patients with a MELD score of less than 20 who underwent hepatic venous pressure gradient (HVPG) measurement. A model named H6C score (= HVPG + 6 × CTP score) to predict overall survival was derived and internal and external validations were conducted with the derivation and validation cohorts.

Results: The H6C score using the HVPG was developed based on a multivariate Cox regression analysis. The H6C score showed a great predictive power for overall survival with a time-dependent AUC of 0.733, which was superior to that of a MELD of 0.602. In patients with viral etiology, the performance of the H6C score was much improved with a time-dependent AUC of 0.850 and was consistently superior to that of the MELD (0.748). Patients with an H6C score below 45 demonstrated an excellent overall survival with a 5-year survival rate of 91.5%. Whereas, patients with an H6C score above 64 showed a dismal prognosis with a 5-year survival rate of 51.1%. The performance of the H6C score was further verified to be excellent in the validation cohort.

Conclusion: This new model using the HVPG provides an excellent predictive power in cirrhotic patients, especially with viral etiology. In patients with H6C above 64, it would be wise to consider early liver transplantation to positively impact long-term survival, even when the MELD score is low.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics10100805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599657PMC
October 2020

Association between Inflammatory Biomarkers and Nutritional Status in Fatty Liver.

Clin Nutr Res 2020 Jul 28;9(3):182-194. Epub 2020 Jul 28.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14854, Korea.

The prevalence and progression of non-alcoholic fatty liver disease (NAFLD) is mediated via several factors correlating with hepatic necroinflammation (adipokines/cytokines). This study was performed to analyze the level of inflammatory markers according to the presence of NAFLD and to identify related nutritional factors. A total of 80 adults were classified into 2 groups (healthy and NAFLD), and their body composition, blood tests, and eating habits were evaluated. In addition, inflammatory markers (adiponectin, high-sensitivity C-reactive protein [CRP], and tumor necrosis factor-alpha [TNF-α]), nutrient intake status, and dietary quality were compared. The quality of diet was assessed according to the nutrient adequacy ratio and the mean adequacy ratio (MAR). The NAFLD group had a higher body mass index (p < 0.001) than the healthy group and also carried significantly higher CRP levels (p < 0.001) but lower adiponectin (p = 0.001). TNF-α levels increased significantly with fatty liver grade (p = 0.023). The NAFLD group showed significantly higher intake of energy, carbohydrates, iron, sodium, vitamin A and saturated fatty acids, but significantly lower intake of zinc and vitamin E than the healthy group. The MAR values were slightly higher in the NAFLD group but without any significant difference. The levels of adiponectin and vitamin E showed a significant inverse correlation (p < 0.05). Nutritional management of NAFLD patients is important, and the intake of antioxidant and anti-inflammatory nutrients such as zinc and vitamin E should be emphasized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7762/cnr.2020.9.3.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402975PMC
July 2020

Risk of fatty liver after long-term use of tamoxifen in patients with breast cancer.

PLoS One 2020 30;15(7):e0236506. Epub 2020 Jul 30.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University School of Medicine Bucheon Hospital, Bucheon, Korea.

Background: Few studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer.

Methods: This was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 consecutive patients were classified into three groups according to treatment method: tamoxifen group, aromatase inhibitor (AI) group, and control group.

Results: Median treatment duration was 49 months (interquartile range, IQR; 32-58) and median observational period was 85 months (IQR; 50-118). Long-term use of tamoxifen significantly aggravated fatty liver status compared to AI or control groups [hazard ratio (HR): 1.598, 95% confidence interval (CI): 1.173-2.177, P = 0.003] after adjusting other factors. When analyzed separately depending on pre-existing fatty liver at baseline, tamoxifen was involved in the development of de novo fatty liver [HR: 1.519, 95% CI: 1.100-2.098, P = 0.011) and had greater effect on fatty liver worsening (HR: 2.103, 95% CI: 1.156-3.826, P = 0.015). However, the progression of fatty liver did not significantly affect the mortality of breast cancer patients.

Conclusions: Tamoxifen had a significant effect on the fatty liver status compared to other treatment modalities in breast cancer patients. Although fatty liver did not affect the prognosis of breast cancer, meticulous attention to cardiovascular disease or other metabolic disease should be paid when used for a long time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236506PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392315PMC
September 2020

Dynamics of liver stiffness-based risk prediction model during antiviral therapy in patients with chronic hepatitis B.

Eur J Gastroenterol Hepatol 2021 Jun;33(6):885-893

Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Bundang.

Objective: The liver stiffness-based risk prediction models predict hepatocellular carcinoma (HCC) development. We investigated the influence of antiviral therapy (AVT) on liver stiffness-based risk prediction model in patients with chronic hepatitis B (CHB).

Methods: Patients with CHB who initiated AVT were retrospectively recruited from 13 referral Korean institutes. The modified risk estimation for hepatocellular carcinoma in chronic hepatitis B (mREACH-B) model was selected for the analysis.

Results: Between 2007 and 2015, 1034 patients with CHB were recruited. The mean age of the study population (639 men and 395 women) was 46.8 years. During AVT, the mREACH-B score significantly decreased from the baseline to 3 years of AVT (mean 9.21 → 7.46, P < 0.05) and was maintained until 5 years of AVT (mean 7.23, P > 0.05). The proportion of high-risk patients (mREACH-B score ≥11) was significantly reduced from the baseline to 2 years of AVT (36.4% → 16.4%, P < 0.001) and was maintained until 5 years of AVT (12.2%, P > 0.05). The mREACH-B scores at baseline and 1 year of AVT independently predicted HCC development (hazard ratio = 1.209-1.224) (all P < 0.05). The cumulative incidence rate of HCC was significantly different at 5 years of AVT among risk groups (high vs. high-intermediate vs. low-intermediate vs. low) from baseline (4.5% vs. 3.2% vs. 1.5% vs. 0.8%) and 1 year (11.8% vs. 4.6% vs. 1.8% vs. 0.6%) (all P < 0.05, log-rank tests).

Conclusions: The mREACH-B score was dynamically changed during AVT. Thus, repeated assessment of the mREACH-B score is required to predict the changing risk of HCC development in patients with CHB undergoing AVT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000001794DOI Listing
June 2021

Clinical application of ultrasonography-guided percutaneous liver biopsy and its safety over 18 years.

Clin Mol Hepatol 2020 07 25;26(3):318-327. Epub 2020 May 25.

Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea.

Background/aims: Liver biopsy (LB) remains the gold standard for the evaluation of liver disease. However, over the past two decades, many noninvasive tests have been developed and utilized in clinical practice as alternatives to LB. The aim of this study was to evaluate the clinical use and safety of LB in the era of noninvasive assessment of liver fibrosis.

Methods: This retrospective study included 1,944 consecutive cases of LB performed between 2001 and 2018 in a tertiary hospital. All of the LBs were conducted under ultrasonography guidance with 18-gauge cutting needles.

Results: LBs were performed an average of approximately 108 times per year during the study period. Chronic hepatitis B (25.3%) and suspected malignancy (20.5%) were the two most common indications for LB. The use of LB for nonalcoholic fatty liver disease increased from 8.1% to 17.2% in the past 5 years compared to the last 10 years, while that for viral hepatitis decreased from 40.3% to 18.9%. Discordance rate between the suspected diagnosis and the final diagnosis was 2.6% (51 cases). The overall rate of major adverse events was 0.05% (one case), which involved delayed bleeding at the biopsy site. Liver cirrhosis was observed in 563 cases (28.9%), and the presence of cirrhosis did not affect the frequency of complications (P=0.289).

Conclusion: LB is widely used in clinical practice as an irreplaceable diagnostic tool, even in the era of noninvasiveness. Ultrasonography-guided LB can be performed safely in patients with liver cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3350/cmh.2019.0019nDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364354PMC
July 2020

Prevalence, incidence and risk factors of tamoxifen-related non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Liver Int 2020 06 7;40(6):1344-1355. Epub 2020 Apr 7.

Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung-si, Korea.

Background & Aims: Tamoxifen is associated with an increased risk of developing fatty liver. The aim of this systematic review and meta-analysis was to evaluate the prevalence and incidence of fatty liver developed after tamoxifen treatment in breast cancer patients.

Methods: A systematic search of PubMed (Medline), EMBASE, OVID Medline, the Cochrane Library and other databases was performed for this review. The abstracts obtained from the search were reviewed by two investigators who chose manuscripts for full-text review. The event rates were calculated with a random-effects model and quality-effects model.

Results: The search yielded 165 references. Of these, 24 were included in the quantitative summary. We analysed the data of a total of 6,962 patients treated with tamoxifen and 975 patients not treated with tamoxifen. The prevalence of fatty liver among patients with breast cancer taking tamoxifen was 40.25 per 100 patients and the incidence rate was 12.37 per 100 person-years. The incidence of fatty liver was much higher in the tamoxifen group than in the control group [incidence rate ratio: 3.12, 95% CI (confidence interval): 2.05-4.75, I  = 61%], regardless of region. The main risk factors were body mass index (BMI) [hazard ratio (HR): 1.15, 95% CI: 1.09-1.22] and hypercholesterolaemia (HR: 1.01, 95% CI: 1.00-1.02).

Conclusion: The use of tamoxifen was associated with increased risks in the incidence and prevalence of fatty liver, especially in patients with high BMI and hypercholesterolaemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14434DOI Listing
June 2020

Change in Portal Pressure and Clinical Outcome in Cirrhotic Patients with Gastric Varices after Plug-Assisted Retrograde Transvenous Obliteration.

Gut Liver 2020 11;14(6):783-791

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.

Background/aims: Plug-assisted retrograde transvenous obliteration (PARTO) is widely used to manage gastric varices with a portosystemic shunt. It is not clear whether portal pressure and the incidence of complications increase after PARTO. The aim of this study was to determine the changes in portal pressure and the associated changes in liver function, ascites, hepatic encephalopathy, and especially esophageal varix (EV) after PARTO.

Methods: From March 2012 to February 2018, 54 patients who underwent PARTO were analyzed retrospectively. The parameters collected included liver function and episodes of cirrhotic complications before and at 1 and 6 months after PARTO.

Results: The analysis of 54 patients showed improvement in liver function during the 6-month follow-up period (Model for End-Stage Liver Disease score: change from 11.46±4.35 to 10.33±2.96, p=0.021). Among these 54 patients, 25 patients were evaluated for their hepatic venous pressure gradient (HVPG) before and after PARTO (change from 12.52±3.83 to 14.68±5.03 mm Hg; p<0.001). Twenty-five patients with portal pressure measured before and after PARTO were evaluated for risk factors affecting liver function improvement and EV deterioration. No factor associated with portal pressure was affected by liver function improvement. Post-PARTO portal pressure was a risk factor affecting EV deterioration (HVPG-post: odds ratio, 1.341; 95% confidence interval, 1.017 to 1.767; p=0.037).

Conclusions: The artificial blockade of the portosystemic shunt evidently leads to an increase in HVPG. Liver function was improved over the 6-month follow-up period. Portal pressure after PARTO was a significant risk factor for EV deterioration. Portal pressure measurement is helpful for predicting the patient's clinical outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5009/gnl19293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667928PMC
November 2020

Propranolol plus endoscopic ligation for variceal bleeding in patients with significant ascites: Propensity score matching analysis.

Medicine (Baltimore) 2020 Jan;99(5):e18913

Department of Internal Medicine, Gangneug Asan Hospital, Republic of Korea.

The use of beta-blockers in decompensated cirrhosis accompanying ascites is still under debate. The aim of this study was to compare overall survival (OS) and incidence of cirrhotic complications between endoscopic variceal ligation (EVL) only and EVL + non-selective beta-blocker (NSBB) combination therapy in cirrhotic patients with significant ascites (≥grade 2).This retrospective study included 271 consecutive cirrhotic patients with ascites who were treated with EVL only or EVL + NSBB combination therapy as a primary prophylaxis of esophageal varices. The primary outcome was all-cause mortality. Propensity score matching was performed between the 2 groups to minimize baseline difference.Median observation period was 42.1 months (interquartile range, 18.4-75.1 months). All patients had deteriorated liver function: 81.1% Child-Pugh class B and 18.9% Child-Pugh class C. All-cause mortality was significantly higher in the EVL + NSBB group than in the EVL only group not only in non-matched cohort, but also in matched cohort (48.9% vs 31.2%; P = .039). More people died from hepatic failure in the EVL + NSBB group than that in the EVL only group (40.5% vs 20.0%; P = .020). However, the incidence of variceal bleeding, hepatorenal syndrome (HRS), or spontaneous bacterial peritonitis (SBP) was not significantly different between the 2 groups.The use of NSBB might worsen the prognosis of cirrhotic patients with significant ascites. These results suggest that EVL alone is a more appropriate treatment option for prophylaxis of esophageal varices than propranolol combination therapy when patients have significant ascites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000018913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004788PMC
January 2020

The Influence of Histologic Inflammation on the Improvement of Liver Stiffness Values Over 1 and 3 Years.

J Clin Med 2019 Nov 24;8(12). Epub 2019 Nov 24.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14854, Korea.

Background: Transient elastography is now an indispensable tool for estimating liver fibrosis. Although many clinical factors other than fibrosis itself are known to affect liver stiffness (LS) values, it is still not yet clear what factors are related to improving LS values. The aim of this study was to find out how baseline histologic inflammation influences LS values and how much this inflammation affects improvement in LS values over time, regardless of actual fibrosis content.

Methods: This retrospective study included 678 consecutive patients who underwent liver biopsy and sequential LS assessment from 2006 to 2015 at six tertiary hospitals in Korea. Linear regression analysis was used to evaluate how improvement of LS value can be associated with other factors besides fibrosis content.

Results: Basal LS values increased with increasing inflammation in the same fibrosis stage. Degree of inflammation influenced the baseline LS value in a proportional manner (beta coefficient (BE), 6.476; 95% confidence interval (CI), 2.24-10.72; = 0.003). Moreover, histologic inflammation affected the change in LS value significantly. Higher inflammation grade at baseline was a significant predictor for an improvement in LS value, regardless of the fibrosis stage (BE, -8.581; 95% CI, -15.715--1.447; = 0.019). In a subgroup analysis of patients who received repeated liver biopsies, the results showed a similar tendency.

Conclusions: The LS value is affected by the degree of inflammation even at a low ALT level. Furthermore, baseline histologic inflammation has a significant impact on the improvement of LS values over time. Therefore, baseline inflammation should be taken into consideration when interpreting an improvement in LS value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8122065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947085PMC
November 2019

Safety profile of sedative endoscopy including cognitive performance in liver cirrhosis: A double-blind randomized controlled trial.

Sci Rep 2019 11 14;9(1):16798. Epub 2019 Nov 14.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University school of medicine Bucheon Hospital, Bucheon, Korea.

The indiscriminate use of sedative drugs during endoscopy can pose multiple risks including cognitive impairment in advanced liver cirrhosis. However, the data are scarce regarding which sedative drugs are safest in these populations. The aim of this study was to evaluate the safety profiles including cognitive performance among midazolam, propofol, and combination therapy in advanced cirrhotic patients. This double-blind randomized controlled study included 60 consecutive advanced cirrhotic patients who underwent upper gastrointestinal endoscopy. The Stroop application was used to screen for cognitive impairment. Patients were randomly assigned to one of 3 groups, midazolam, propofol, or the combination group, and underwent Stroop test before and two hours after the completion of endoscopy. Hemodynamic safety and the subjective satisfaction score were also evaluated. Patients did not show significant changes in on-time or off-time on the Stroop test before and two hours after sedatives, and there was no significant difference among the 3 treatment groups. Also, there were no significant vital sign changes after sedatives. Time-to-recovery was longest in midazolam group, and patient awakening and patient memory were highest in propofol group. However, all 3 groups showed no difference in patient satisfaction, but the combination group was more preferred in terms of subjective satisfaction by physicians. Factors affecting worsened Stroop speed after sedatives were older age, low education level and high MELD score. All sedative methods using midazolam, propofol, or combination therapy showed similar safety profile in advanced cirrhosis, and were not associated with increased risk of cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-52897-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856546PMC
November 2019

Correlation of the grade of hepatic steatosis between controlled attenuation parameter and ultrasound in patients with fatty liver: a multi-center retrospective cohort study.

Korean J Intern Med 2020 11 8;35(6):1346-1353. Epub 2019 Nov 8.

Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

Background/aims: The controlled attenuation parameter (CAP), based on transient elastography, is widely used for noninvasive assessment of the degree of hepatic steatosis (HS). We investigated the correlation of the degree HS between CAP and ultrasound (US) in patients with HS.

Methods: In total, 986 patients with US-based HS who underwent transient elastography within 1 month were evaluated. The US-based grade of HS was categorized as mild (grade 1), moderate (grade 2), or severe (grade 3).

Results: The CAP was significantly correlated with the US-based grade of HS (r = 0.458, p < 0.001). The median CAP value of each US-based HS grade showed a positive correlation with grade (271.1, 303.7, and 326.7 dB/m for grades 1, 2, and 3). In a multivariate analysis, the US-based HS grade, body mass index, serum albumin, alanine aminotransferase, and total cholesterol, and liver stiffness were all significantly correlated with the CAP value (all p < 0.05). The areas under the receiver operating characteristic curves for grade 2 to 3 and grade 3 HS were 0.749 (95% confidence interval [CI], 0.714 to 0.784) and 0.738 (95% CI, 0.704 to 0.772). The optimal cut-off CAP values to maximize the sum of the sensitivity and specificity for grade 2 to 3 and grade 3 HS were 284.5 dB/m (sensitivity 78.6%, specificity 61.7%) and 298.5 dB/m (sensitivity 84.6%, specificity 55.6%).

Conclusion: The correlation of the degree of HS between CAP and US was significantly high in patients with HS, and the optimal cut-off CAP values for grade 2 to 3 and grade 3 HS were 284.5 and 298.5 dB/m.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3904/kjim.2018.309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652655PMC
November 2020

Appraisal of a Model to Estimate Survival in Ambulatory Patients with Hepatocellular Carcinoma Classified as Barcelona Clinic Liver Cancer Stage B.

Gut Liver 2020 05;14(3):377-386

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Background/aims: Patients with an intermediate stage of hepatocellular carcinoma (HCC) represent a highly heterogeneous population; therefore, many models have been proposed to predict the survival of these patients. The aim of this study was to evaluate the prognostic performance of a novel subclassification for tumors classified as Barcelona Clinic Liver Cancer (BCLC) stage B using the Model to Estimate Survival in Ambulatory HCC patients (MESIAH).

Methods: This analysis was based on 377 patients with HCC treated at Seoul National University Hospital (training cohort) and 189 patients at the Soonchunhyang University Bucheon Hospital (validation cohort). Four subclassification systems were tested: MESIAH; original BCLC B subclassification (B1, B2, B3, and B4); modified model A (B1, B2, and B3+B4); and modified model B (B1, B2+B3, and B4).

Results: Median survival progressively decreased from stage B1 through stages B2 to B3 according to the new MESIAH subclassification (p<0.001). Moreover, significantly different survival among contiguous stages was observed. In the multivariable Cox regression, the MESIAH subclassification was an independent predictor of overall survival (p<0.001). In terms of discrimination and calibration, MESIAH performed better than the original BCLC B subclassification, modified model A and modified model B.

Conclusions: The MESIAH model would be an effective tool for stratifying heterogeneous BCLC stage B cancer, and the ability of this model to predict survival is better than that of the other previously proposed models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5009/gnl19112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234889PMC
May 2020

HVPG as a Predictor of Mortality in Non-Critically-Ill Cirrhotic Patients.

J Korean Med Sci 2019 08 26;34(33):e235. Epub 2019 Aug 26.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University School of Medicine Bucheon Hospital, Bucheon, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3346/jkms.2019.34.e235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706352PMC
August 2019

Intraductal placement of non-flared fully covered metallic stent for refractory anastomotic biliary strictures after living donor liver transplantation: Long-term results of prospective multicenter trial.

J Gastroenterol Hepatol 2020 Mar 10;35(3):492-498. Epub 2019 Sep 10.

Department of Internal Medicine, SoonChunHyang University School of Medicine, Cheonan, Korea.

Background And Aim: Fully covered self-expandable metallic stent (FCSEMS) may be an effective modality for managing anastomotic biliary stricture (ABS) after liver transplantation. However, stent migration and stent-induced ductal injury are the main limitations. The objective of this study was to evaluate the usefulness of an unflared, intraductal FCSEMS that was designed to minimize migration and ductal injury for refractory ABS after living donor liver transplantation (LDLT).

Methods: A total of 32 consecutive patients with symptomatic ABS after LDLT unresolved by plastic stents with or without balloon dilation at four tertiary medical centers were prospectively enrolled. A short (3 or 5 cm) FCSEMS having long lasso (10 cm) used in this study had unflared convex ends to minimize tissue hyperplasia and smaller center portion to prevent migration. The FCSEMS was placed above the papilla and removed at 3-4 months after stenting.

Results: Technical and clinical success rates of intraductal placement with FCSEMS were 100% (32/32) and 81.2% (26/32), respectively. Early stent migration was observed in five (15.6%) patients. However, three patients with early stent migration had stricture resolution without needing additional intervention. Intended stent removal was successful in 27 (100%) patients (median, 101 days; range, 23-118 days). No stent-induced ductal change was observed in all patients. Stricture recurrence was observed in 11.5% (3/26) of patients during 639 days of median duration of follow-up (range, 366-2079 days).

Conclusions: Intraductal placement of an unflared short FCSEMS may be a promising option for refractory ABS after LDLT with minimal stent-induced ductal injury and stent migration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.14831DOI Listing
March 2020

Usefulness of noninvasive methods including assessment of liver stiffness by 2-dimensional shear wave elastography for predicting esophageal varices.

Dig Liver Dis 2019 12 4;51(12):1706-1712. Epub 2019 Jul 4.

Division of Gastroenterology and Hepatology, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea.

Background: The aim of this study was to predict the presence of esophageal varices (EVs) by noninvasive tools combined with 2-dimensional shear wave elastography (2D-SWE), and to compare the diagnostic capabilities of 2D-SWE with those of transient elastography (TE).

Methods: Between January 2015 and December 2017, 289 patients with compensated advanced chronic liver disease (cACLD) who underwent consecutive 2D-SWE and EGD were enrolled. Capabilities for predicting the presence of EVs of 2D-SWE and models combining 2D-SWE with other noninvasive tools (modified LS-spleen-diameter-to-platelet-ratio score [mLSPS], platelet-spleen ratio score) were compared. A subgroup analysis was performed on 177 patients who also underwent simultaneous TE.

Results: The area under receiver operating characteristics (AUROCs) for detecting EVs for 2D-SWE alone vs. mLSPS, which included 2D-SWE, were 0.757 (95% confidence interval [CI], 0.701-0.810) and 0.813 (95% CI, 0.763-.857), respectively. The AUROCs for predicting varices needing treatment (VNT) for 2D-SWE and mLSPS were 0.712 (95% CI, 0.621-0.738) and 0.834 (95% CI, 0.785-0.875), respectively. For the 195 patients who underwent simultaneous TE and 2D-SWE, no differences in diagnostic performance were observed.

Conclusions: The diagnostic performance of 2D-SWE is similar to that of TE for predicting the presence of EVs. The mLSPS, which includes 2D-SWE, seemed to be useful for predicting EVs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2019.06.007DOI Listing
December 2019

Hexokinase-II Inhibition Synergistically Augments the Anti-tumor Efficacy of Sorafenib in Hepatocellular Carcinoma.

Int J Mol Sci 2019 Mar 14;20(6). Epub 2019 Mar 14.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea.

This study aimed to examine whether inhibition of hexokinase (HK)-II activity enhances the efficacy of sorafenib in in-vivo models of hepatocellular carcinoma (HCC), and to evaluate the prognostic implication of HK-II expression in patients with HCC. We used 3-bromopyruvate (3-BP), a HK-II inhibitor to target HK-II. The human HCC cell line was tested as both subcutaneous and orthotopic tumor xenograft models in BALB/c nu/nu mice. The prognostic role of HK-II was evaluated in data from HCC patients in The Cancer Genome Atlas (TCGA) database and validated in patients treated with sorafenib. Quantitative real-time PCR, western blot analysis, and immunohistochemical staining revealed that HK-II expression is upregulated in the presence of sorafenib. Further analysis of the endoplasmic reticulum-stress network model in two different murine HCC models showed that the introduction of additional stress by 3-BP treatment synergistically increased the in vivo/vitro efficacy of sorafenib. We found that HCC patients with increased HK-II expression in the TCGA database showed poor overall survival, and also confirmed similar results for TCGA database HCC patients who had undergone sorafenib treatment. These results suggest that HK-II is a promising therapeutic target to enhance the efficacy of sorafenib and that HK-II expression might be a prognostic factor in HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20061292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471302PMC
March 2019

Identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients.

J Hepatol 2019 06 20;70(6):1093-1102. Epub 2019 Feb 20.

Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Republic of Korea; KU Open Innovation Center, Konkuk University, Seoul, Republic of Korea; Research Institute of Medical Sciences, Konkuk University, Seoul, Republic of Korea. Electronic address:

Background & Aims: Tenofovir disoproxil fumarate (TDF) is one the most potent nucleot(s)ide analogues for treating chronic hepatitis B virus (HBV) infection. Phenotypic resistance caused by genotypic resistance to TDF has not been reported. This study aimed to characterize HBV mutations that confer tenofovir resistance.

Methods: Two patients with viral breakthrough during treatment with TDF-containing regimens were prospectively enrolled. The gene encoding HBV reverse transcriptase was sequenced. Eleven HBV clones harboring a series of mutations in the reverse transcriptase gene were constructed by site-directed mutagenesis. Drug susceptibility of each clone was determined by Southern blot analysis and real-time PCR. The relative frequency of mutants was evaluated by ultra-deep sequencing and clonal analysis.

Results: Five mutations (rtS106C [C], rtH126Y [Y], rtD134E [E], rtM204I/V, and rtL269I [I]) were commonly found in viral isolates from 2 patients. The novel mutations C, Y, and E were associated with drug resistance. In assays for drug susceptibility, the IC value for wild-type HBV was 3.8 ± 0.6 µM, whereas the IC values for CYE and CYEI mutants were 14.1 ± 1.8 and 58.1 ± 0.9 µM, respectively. The IC value for wild-type HBV was 30 ± 0.5 µM, whereas the IC values for CYE and CYEI mutants were 185 ± 0.5 and 790 ± 0.2 µM, respectively. Both tenofovir-resistant mutants and wild-type HBV had similar susceptibility to the capsid assembly modulator NVR 3-778 (IC <0.4 µM vs. IC = 0.4 µM, respectively).

Conclusions: Our study reveals that the quadruple (CYEI) mutation increases the amount of tenofovir required to inhibit HBV by 15.3-fold in IC and 26.3-fold in IC. These results demonstrate that tenofovir-resistant HBV mutants can emerge, although the genetic barrier is high.

Lay Summary: Tenofovir is the most potent nucleotide analogue for the treatment of chronic hepatitis B virus infection and there has been no hepatitis B virus mutation that confers >10-fold resistance to tenofovir up to 8 years. Herein, we identified, for the first time, a quadruple mutation that conferred 15.3-fold (IC) and 26.3-fold (IC) resistance to tenofovir in 2 patients who experienced viral breakthrough during tenofovir treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2019.02.006DOI Listing
June 2019

Estimation of renal function in patients with liver cirrhosis: Impact of muscle mass and sex.

J Hepatol 2019 05 8;70(5):847-854. Epub 2019 Jan 8.

Department of Internal Medicine, Gangneung Asan Hospital, Gangneung, Republic of Korea.

Background & Aims: Accurate evaluation of renal function in patients with liver cirrhosis is critical for clinical management. However, there are still discrepancies between the measured glomerular filtration rate (mGFR) and creatinine-based estimated GFR (eGFR). In this study, we compared the performance of 2 common eGFR measurements with mGFR and evaluated the impact of low muscle mass on overestimation of renal function in patients with cirrhosis.

Methods: This study included 779 consecutive cirrhotic patients who underwent Cr-ethylenediamine tetra acetic acid (EDTA) (as a mGFR) and abdominal computed tomography (CT). The eGFR was calculated using creatinine or cystatin C. Muscle mass was assessed in terms of the total skeletal muscle at L3 level using CT.

Results: Modification of diet in renal disease (MDRD)-eGFR was overestimated in 47% of patients. A multivariate analysis showed that female sex (adjusted odds ratio [aOR] 4.91), Child B and C vs. A (aOR 1.69 and 1.84) and skeletal muscle mass (aOR 0.89) were independent risk factors associated with overestimation. Interestingly, the effect of skeletal muscle mass on overestimation varied based on sex. Decreased muscle mass significantly enhanced the risk of overestimation of MDRD-eGFR in male patients, but not in female patients. Cystatin C-based eGFR showed a better correlation with mGFR than MDRD-eGFR; it was also better at predicting overall survival and the incidence of acute kidney injury than MDRD-eGFR.

Conclusions: The risk factors associated with overestimation included female sex, impaired liver function, and decreased muscle mass in males. In particular, eGFR in male patients with sarcopenia should be carefully interpreted. Creatinine-based eGFR was overestimated more often than cystatin C-based eGFR, with overestimation of eGFR closely related to poor prognostic performance.

Lay Summary: Overestimation of renal function frequently occurs in patients with liver cirrhosis when using serum creatinine. Decreased muscle mass has a great impact on overestimation of kidney function especially in male patients with cirrhosis. Compared with creatinine, cystatin C was more closely correlated with measured glomerular filtration rate and had a higher predictive ability for renal complications and survival than creatinine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2018.12.030DOI Listing
May 2019
-->