Pancreatic beta-cell mass and function and therapeutic implications of using antidiabetic medications in type 2 diabetes.

Nowadays, the focus of diabetes treatment has switched from lowering the glucose level to preserving glycemic homeostasis and slowing the disease progression. The main pathophysiology of both type 1 diabetes and long-standing type 2 diabetes is pancreatic ß-cell mass loss and dysfunction. According to recent research, human pancreatic ß-cells possess the ability to proliferate in response to elevated insulin demands. It has been demonstrated that in insulin-resistant conditions in humans, such as obesity or pregnancy, the ß-cell mass increases. This ability could be helpful in developing novel treatment approaches to restore a functional ß-cell mass. Treatment strategies aimed at boosting ß-cell function and mass may be a useful tool for managing diabetes mellitus and stopping its progression. This review outlines the processes of ß-cell failure and detail the many ß-cell abnormalities that manifest in people with diabetes mellitus. We also go over standard techniques for determining the mass and function of ß-cells. Lastly, we provide the therapeutic implications of utilizing antidiabetic drugs in controlling the mass and function of pancreatic ß-cells.

Steatotic liver disease predicts cardiovascular disease and advanced liver fibrosis: A community-dwelling cohort study with 20-year follow-up.

BACKGROUND: Steatotic liver disease (SLD) has emerged as new nomenclature to increase awareness and reflect the pathophysiology of the disease better. We investigated the risk of advanced fibrosis and cardiovascular disease (CVD) in SLD using data derived from a Korean prospective cohort. METHODS: We defined SLD using the fatty liver index (FLI) and identified advanced fibrosis with the age-adjusted Fibrosis-4 Index. SLD was further subcategorized into metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD). FINDINGS: The Ansung-Ansan cohort of the Korean Genome and Epidemiology study, following 9497 participants from 2002 to 2020, included 3642 (38.3%) with MASLD, 424 (4.5%) with MetALD, and 207 (2.1%) with ALD. During the median follow-up of 17.5 years, CVD risk was higher in those with MASLD (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.12-1.45; P < 0.001), MetALD (HR, 1.88; 95% CI, 1.33-2.65; P < 0.001), and ALD (HR, 1.95; 95% CI, 1.01-3.77; P < 0.001) than in those without SLD, after adjusting for conventional risk factors. Notably, CVD risk was higher in the MetALD than in the MASLD group (P = 0.027). In the MASLD group, the number of cardiometabolic risk factors (CMRFs) correlated positively with CVD risk (HR, 1.34; 95% CI, 1.24-1.45; P < 0.001 for trend). Among the CMRFs, hypertension (HR, 1.94; 95% CI, 1.63-2.31; P < 0.001) was the predominant contributor to CVD. The MASLD (HR, 1.39; 95% CI, 1.25-1.55; P < 0.001), MetALD (HR, 1.75; 95% CI, 1.38-2.23; P < 0.001), and ALD (HR, 2.00; 95% CI, 1.30-3.07; P = 0.002) groups had a higher risk of advanced fibrosis than did the non-SLD group (P < 0.001 for trend). INTERPRETATION: Our study provides new insight into hepatic and cardiovascular outcomes related to SLD subtypes. The risk of CVD increased in the order of no SLD, MASLD, and MetALD. The SLD subcategories, considering CMRFs and alcohol intake, outperformed traditional fatty liver categorizations in predicting CVD risk. The proposed SLD terminology could impact clinical practice, warranting further exploration of the heterogeneity of clinical outcomes among SLD subtypes.

Independent association of thigh muscle fat density with vascular events in Korean adults.

BACKGROUND: We aimed to explore the associations between thigh muscle fat density and vascular events. METHODS: A total of 3,595 adults (mean age, 57.2 years; women, 1,715 [47.7%]) without baseline cardiovascular events from the Korean Atherosclerosis Study-2 were included. Muscle and fat area at the mid-thigh level were measured by computed tomography (CT) using the following Hounsfield Unit range: 0-30 for low density muscle (LDM); 31-100 for normal density muscle (NDM); and - 250 to - 50 for fat. RESULTS: During a median follow-up period of 11.8 (4.3-13.9) years, vascular events occurred in 11.6% of men and 5.9% of women. Individuals with vascular events had a larger LDM area (men: 48.8 ± 15.5 cm2 vs. 44.6 ± 14.5 cm2; women: 39.4 ± 13.2 cm2 vs. 35.0 ± 11.8 cm2, both P < 0.001) compared with those who did not have vascular events during the follow-up of at least 5 years. The LDM/NDM ratio was also independently associated with vascular events after adjusting for cardiometabolic risk factors. Moreover, the LDM/NDM ratio improved the prognostic value for vascular events when added to conventional risk factors. CONCLUSIONS: The current study suggests that a higher thigh muscle fat infiltration is associated with an increased risk of developing vascular events among Korean adults.

SUMO-specific protease 2 regulates lipid droplet size through ERRα-mediated CIDEA expression in adipocytes.

Lipid droplets are not only lipid storage sites but also are closely related to lipid metabolism. Lipid droplet growth increases lipid storage capacity and suppresses lipolysis via lipase associated with the lipid droplet surface. The cell death-inducing DFF45-like effector (CIDE) family of proteins mediates lipid droplet fusion, which mainly contributes to lipid droplet growth. We previously demonstrated small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) plays important roles in lipid metabolism and induction/maintenance of adipogenesis. In this study, we determined whether SENP2 regulates lipid droplet size in adipocytes. Overexpression of SENP2 increased lipid droplet size in differentiated 3T3-L1 adipocytes and facilitated CIDEA transcription. We found SENP2 increased CIDEA expression mainly through desumoylation of estrogen-related receptor α (ERRα), which acted in coordination with peroxisome proliferator-activated receptor γ-coactivator α. In addition, palmitate treatment increased SENP2 and CIDEA mRNA levels. Specific small interfering RNA-mediated knockdown of SENP2, as well as ERRα knockdown, eliminated palmitate-induced CIDEA expression. These results suggest SENP2 enhances CIDEA expression by modulating ERRα when SENP2 is upregulated, such as after palmitate treatment, to increase lipid droplet size in adipocytes.

Different effects of low muscle mass on the risk of non-alcoholic fatty liver disease and hepatic fibrosis in a prospective cohort.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and sarcopenia share insulin resistance as a common pathophysiology and have overlapping clinical manifestation of metabolic derangement; hence, it is difficult to differentiate the independent effect of sarcopenia on the development of NAFLD from concomitant metabolic disorders. Using a community-based prospective cohort study, the contributions of low muscle mass and genetic risk factors to the development of NAFLD and NAFLD-related hepatic fibrosis were investigated in the Korean population. METHODS: This prospective community-based cohort study included 40-70-year-old adults, followed up biennially from 2001-2002 to 2017-2018. NAFLD was defined as a hepatic steatosis index of ≥36, and hepatic fibrosis was defined based on the fibrosis-4 index. Sex-specific quartiles of body mass index (BMI)-adjusted muscle mass were calculated (muscle mass/BMI), and low muscle mass was defined as the lowest quartile (Q1). Cox proportional hazard models for incident NAFLD or hepatic fibrosis incorporating age, sex, BMI of ≥25 kg/m2 , metabolic syndrome and PNPLA3 and TM6SF2 risk alleles were used to assess the independent determinants for incident NAFLD and hepatic fibrosis among individuals with NAFLD at baseline. RESULTS: Among the 4038 participants without NAFLD at baseline (mean age, 51.5 ± 8.8 years), 920 (22.8%) developed NAFLD during the 12-year follow-up period. As muscle mass decreased, the risk of NAFLD increased even after adjustment for age, sex, obesity, metabolic syndrome and PNPLA3 and TM6SF2 risk alleles [hazard ratio (HR) per quartile, 1.18, 95% confidence interval (CI), 1.11-1.27, P < 0.001]. TM6SF2 also affected the risk of NAFLD development [HR 1.19, (95% CI, 1.00-1.40), P = 0.044]. Of the 1176 patients with NAFLD but without hepatic fibrosis at baseline, the incident of hepatic fibrosis was found in 51.8%, 44.7%, 42.6% and 41.0% in Q1, Q2, Q3 and Q4 of BMI-adjusted muscle mass, respectively, during the follow-up period (P for trend = 0.006). However, this trend lost its statistical significance when adjusted for confounders. The PNPLA3 risk variant, but not the TM6SF2 genotype, was an independent risk factor for developing hepatic fibrosis among patients with NAFLD (HR 1.17, 95% CI 1.04-1.32, P = 0.010). CONCLUSIONS: Both lower muscle mass index and genetic risk variants are important contributors to the development of NAFLD. In patients already diagnosed with NAFLD, however, PNPLA3 confers a greater risk for hepatic fibrosis progression than lower muscle mass.

Effects of Patient-Driven Lifestyle Modification Using Intermittently Scanned Continuous Glucose Monitoring in Patients With Type 2 Diabetes: Results From the Randomized Open-label PDF Study.

OBJECTIVE: To investigate the effects of patient-driven lifestyle modification using intermittently scanned continuous glucose monitoring (isCGM) in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We conducted a 12-week, open-label, randomized controlled trial. A total of 126 participants were 1:1 randomized to either the intervention group (structured education + isCGM) or the control group (standard care with blood glucose monitoring). The Self-Evaluation Of Unhealthy foods by Looking at postprandial glucose (SEOUL) algorithm was developed and applied to aid structured education in guiding patients to follow healthy eating behavior depending on the postprandial glycemic response. The primary end point was the change in HbA1c level from baseline. RESULTS: Implementation of the SEOUL algorithm with isCGM was associated with greater improvement in HbA1c than with standard care (risk-adjusted difference -0.50%, 95% CI -0.74 to -0.26, P < 0.001). Participants in the intervention group had a greater reduction in fasting blood glucose and body weight (-16.5 mg/dL, 95% CI -30.0 to -3.0, P = 0.017; -1.5 kg, 95% CI -2.7 to -0.3, P = 0.013, respectively). The score sum for the Korean version of the revised Summary of Diabetes Self-Care Activities Questionnaire increased in both groups but to a greater extent in the intervention group (mean difference 4.8, 95% CI 1.7-8.0, P = 0.003). No severe hyperglycemia or hypoglycemia was reported in either group of patients. CONCLUSIONS: Patient-driven lifestyle modification primarily focused on eating behavior using isCGM effectively lowered HbA1c levels in patients with T2D.

Gender differences in risk factors for the 2 year development of sarcopenia in community-dwelling older adults.

BACKGROUND: Sarcopenia is an age-related chronic condition that can lead to mobility disabilities. This study aimed to evaluate the risk factors for incident sarcopenia in older Korean adults. METHODS: The Korean Frailty and Aging Cohort Study (KFACS) is a multicentre prospective study with a baseline examination in 2016-2017. A prospective follow-up study was conducted in 2018-2019. Changes in muscle-related variables were evaluated for subjects aged 70-84 years lacking sarcopenia at baseline. Sarcopenia was diagnosed according to the 2019 updated Asian Working Group for Sarcopenia consensus. RESULTS: Among the 1636 participants (54.4% women, age 75.9 ± 3.7) who did not have sarcopenia at baseline, 101 men (13.5%) and 104 women (11.7%) developed sarcopenia by the follow-up. Those who developed sarcopenia were older (men, 77.9 ± 3.9 vs. 75.7 ± 3.5, P < 0.001; women, 77.5 ± 4.0 vs. 75.5 ± 3.6, P < 0.001) with a lower body mass index at baseline (men, 23.9 ± 2.4 vs. 24.5 ± 2.9 kg/m2 , P = 0.025; women, 23.7 ± 2.8 vs. 25.2 ± 2.9 kg/m2 , P < 0.001) compared with older adults who remained nonsarcopenic; levels of glycated haemoglobin (men, 6.2 ± 1.0% vs. 5.9 ± 0.8%, P = 0.029) and the homeostasis model assessment of insulin resistance (men, 2.0 ± 1.3 vs. 1.7 ± 1.2, P = 0.022) were higher in men who progressed to sarcopenia but not in women. Development of sarcopenia was associated with older age and the frequency of resistance training (≥2 per week) after adjusting for potential risk factors in men [age, odds ratio (OR) 1.17, 95% confidence interval (CI) 1.10-1.25; frequent resistance training, OR 0.50, 95% CI 0.30-0.82]. In women, advanced age, poor nutritional status, and physical inactivity contributed to the development of sarcopenia (age, OR 1.14, 95% CI 1.08-1.21; mini nutritional assessment short form, OR 0.79, 95% CI 0.70-0.90; moderate to high physical activity, OR 0.57, 95% CI 0.34-0.95). CONCLUSIONS: In this 2 year KFACS follow-up, modifiable risk factors for incident sarcopenia differed between genders. Resistance training (≥2 per week) helped to prevent sarcopenia in these community-dwelling older men. In older women, adequate nutritional support and being physically active might play a role in preventing progression to sarcopenia.

Association of vitamin D status with COVID-19 and its severity : Vitamin D and COVID-19: a narrative review.

Vitamin D is associated with biological activities of the innate and adaptive immune systems, as well as inflammation. In observational studies, an inverse relationship has been found between serum 25-hydroxyvitamin D (25(OH)D) concentrations and the risk or severity of coronavirus disease 2019 (COVID-19). Several mechanisms have been proposed for the role of vitamin D in COVID-19, including modulation of immune and inflammatory responses, regulation of the renin-angiotensin-aldosterone system, and involvement in glucose metabolism and cardiovascular system. Low 25(OH)D concentrations might predispose patients with COVID-19 to severe outcomes not only via the associated hyperinflammatory syndrome but also by worsening preexisting impaired glucose metabolism and cardiovascular diseases. Some randomized controlled trials have shown that vitamin D supplementation is beneficial for reducing severe acute respiratory syndrome coronavirus 2 RNA positivity but not for reducing intensive care unit admission or all-cause mortality in patients with moderate-to-severe COVID-19. Current evidence suggests that taking a vitamin D supplement to maintain a serum concentration of 25(OH)D of at least 30 ng/mL (preferred range 40-60 ng/mL), can help reduce the risk of COVID-19 and its severe outcomes, including mortality. Although further well designed studies are warranted, it is prudent to recommend vitamin D supplements to people with vitamin D deficiency/insufficiency during the COVID-19 pandemic according to international guidelines.

Comparison of Prevailing Insulin Regimens at Different Time Periods in Hospitalized Patients: A Real-World Experience from a Tertiary Hospital.

BACKGROUND: Prevailing insulin regimens for glycemic control in hospitalized patients have changed over time. We aimed to determine whether the current basal-bolus insulin (BBI) regimen is superior to the previous insulin regimen, mainly comprising split-mixed insulin therapy. METHODS: This was a single tertiary center, retrospective observational study that included non-critically ill patients with type 2 diabetes mellitus who were treated with split-mixed insulin regimens from 2004 to 2007 (period 1) and with BBI from 2008 to 2018 (period 2). Patients from each period were analyzed after propensity score matching. The mean difference in glucose levels and the achievement of fasting and preprandial glycemic targets by day 6 of admission were assessed. The total daily insulin dose, incidence of hypoglycemia, and length of hospital stay were also evaluated. RESULTS: Among 244 patients from each period, both fasting glucose (estimated mean±standard error, 147.4±3.1 mg/dL vs. 129.4±3.2 mg/dL, P<0.001, day 6) and preprandial glucose (177.7±2.8 mg/dL vs. 152.8±2.8 mg/dL, P<0.001, day 6) were lower in period 2 than in period 1. By day 6 of hospital admission, 42.6% and 67.2% of patients achieved a preprandial glycemic target of <140 mg/dL in periods 1 and 2, respectively (relative risk, 2.00; 95% confidence interval, 1.54 to 2.59), without an increased incidence of hypoglycemia. Length of stay was shorter in period 2 (10.23±0.26 days vs. 8.70±0.26 days, P<0.001). CONCLUSION: BBI improved glycemic control in a more efficacious manner than a split-mixed insulin regimen without increasing the risk of hypoglycemia in a hospital setting.

Skeletal effects of combined bisphosphonates treatment and parathyroidectomy in osteoporotic patients with primary hyperparathyroidism.

INTRODUCTION: Bone loss caused by primary hyperparathyroidism (PHPT) is an indication for parathyroidectomy (PTX). However, whether adding bisphosphonates would be superior to PTX alone to increase bone mass remains unclear. We thus aimed to compare the skeletal effects of the combination treatment of bisphosphonates and PTX with PTX alone. MATERIALS AND METHODS: In this retrospective analysis, bone mineral density (BMD) changes after 1 year of combination treatment and PTX alone were compared. We also analyzed the correlation between changes in serum biochemical parameters and BMD after 1 year of treatment in both groups. RESULTS: The baseline characteristics of patients treated with PTX alone (n = 24) and combination treatment (n = 26) were comparable. BMD significantly increased after 1 year of treatment in both groups (all p < 0.001), and the increase in BMD at the femur neck was higher in the PTX alone group than in the combination group (p = 0.011). There was a decreasing trend in serum alkaline phosphatase (ALP) levels in PTX alone compared to the combination treatment group (p = 0.053). In the study cohort, lower BMD and higher ALP levels at baseline were associated with higher 1-year BMD changes at all sites. Interestingly, a significant association was found between changes in ALP and BMD at the femur neck in the PTX alone group (p = 0.003), but abolished in the combination group (p = 0.946). CONCLUSIONS: There is no additional benefit of BMD in combination treatment with bisphosphonates and PTX over PTX alone in osteoporotic patients with PHPT. Combined bisphosphonate treatment might interfere with the increase in bone mass caused by PTX.

Contribution of hypertriglyceridemia to ischemic cardiovascular disease in Korean women: A nationwide population-based study.

BACKGROUND: The independent effect of serum triglyceride levels on the development of ischemic cardiovascular disease (CVD) remains inconclusive, which might be due to heterogeneity among study populations. OBJECTIVE: To evaluate the effect of triglyceride levels on ischemic CVD and mortality in Korean women, with stratification according to the menopausal status, diabetes mellitus, or low-density lipoprotein cholesterol levels (LDL-C). METHODS: We retrospectively investigated Korean women aged 40-69 years who underwent health examination in 2009 and were followed up until 2018 using nationwide claim data. The subjects were divided according to triglyceride quartiles (Q): Q1 <70 mg/dL, Q2 71-99 mg/dL, Q3 100-142 mg/dL, and Q4 ≥143 mg/dL. The primary outcome was the incidence of CVD defined as a composite of myocardial infarction and ischemic stroke. RESULTS: Among 2,208,347 women, primary outcome occurred in 62,255 (2.8%) subjects. As triglyceride levels increased, the event rate of primary outcome increased in both premenopausal and postmenopausal women in the fully adjusted model (hazard ratio [HR] per 1 Q, 1.10 [95% confidence interval (CI), 1.08-1.12] and 1.08 [95% CI, 1.07-1.09], respectively), which was maintained on further stratification according to diabetes or LDL-C (P<0.05 in all). Higher triglyceride levels were more significantly associated with the primary outcome, MI, and stroke risk among women with optimal non-high-density lipoprotein cholesterol levels (non-HDL-C) <130 mg/dL, but only weakly with stroke for women with non-optimal non-HDL-C. CONCLUSION: Triglyceride is an independent prognosticator in the development of ischemic CVD in Korean women aged 40-69 years.

Peptidyl and Non-Peptidyl Oral Glucagon-Like Peptide-1 Receptor Agonists.

Glucagon-like peptide-1 (GLP-1) receptor agonists are efficacious glucose-lowering medications with salient benefits for body weight and cardiovascular events. This class of medications is now recommended as the top priority for patients with established cardiovascular disease or indicators of high risk. Until the advent of oral semaglutide, however, GLP-1 receptor agonists were available only in the form of subcutaneous injections. Aversion to needles, discomfort with self-injection, or skin problems at the injection site are commonly voiced problems in people with diabetes, and thus, attempts for non-invasive delivery strategies have continued. Herein, we review the evolution of GLP-1 therapy from its discovery and the development of currently approved drugs to the unprecedented endeavor to administer GLP-1 receptor agonists via the oral route. We focus on the pharmacokinetic and pharmacodynamic properties of the recently approved oral GLP-1 receptor agonist, oral semaglutide. Small molecule oral GLP-1 receptor agonists are currently in development, and we introduce how these chemicals have addressed the challenge posed by interactions with the large extracellular ligand binding domain of the GLP-1 receptor. We specifically discuss the structure and pharmacological properties of TT-OAD2, LY3502970, and PF-06882961, and envision an era where more patients could benefit from oral GLP-1 receptor agonist therapy.

Acute pulmonary thromboembolism caused by factor V Leiden mutation in South Korea: A case report.

RATIONALE: Although Factor V Leiden (FVL) mutation is a major cause of inherited thrombophilia in Western populations; the mutation is extremely rare in Asia. PATIENT CONCERNS: Here we report a case of a 28-year old Korean woman admitted to our hospital with extensive pulmonary embolism. DIAGNOSIS: She was heterozygous for FVL mutation up on evaluation, and screening for asymptomatic family members also revealed heterozygous FVL mutation for her mother. INTERVENTIONS: Enoxaparin 1 mg/kg was initiated, followed by rivaroxaban 15 mg every 12 hours. OUTCOMES: The patient showed improvement in both subjective dyspnea and right ventricular dysfunction and was successfully discharged after five hospital days. LESSONS: FVL mutation screening may be considered in Asian patients with thrombophilia of uncertain etiology in the future.

Acute liver failure caused by occupational exposure to HCFC-123: Two case reports.

RATIONALE: Hydrochlorofluorocarbon 123 (HCFC-123, Freon123; 2,2-dichloro-1,1,1-trifluoroethane) has been widely used in refrigeration and heat-transfer applications as a substitute for chlorofluorocarbons due to its lower ozone-depleting potentials. Occupational exposure to HCFC-123 may cause mild reversible hepatoxicity, but no fatal cases have been reported yet. PATIENT CONCERNS: In this report, we present cases of severe hepatitis with fatal outcome by HCFC-123. Two industrial workers from a manufacturing factory of fire extinguishers which use HCFC-123 were presented with diarrhea, fever, myalgia, and jaundice. Patients had been repeatedly exposed to the liquid form of HCFC-123 for the past three weeks before flare of symptoms. DIAGNOSIS: The blood biochemistry tests showed acute cholestatic hepatitis and liver biopsy findings indicated inflammatory hepatocellular injury. The diagnosis of HCFC-123 induced hepatitis was made. INTERVENTIONS: The treatment for both patients were generally supportive. The second patient went through hemodialysis, ventilatory care, and artificial liver support therapy (molecular adsorbent recirculating system) at intensive care unit. OUTCOMES: One patient recovered uneventfully, whereas the other patient showed rapid deterioration leading to acute liver failure complicated with cerebral edema, subdural hemorrhage, and death on hospital day 10. LESSONS: The HCFC-123-induced hepatitis showed similarities with halothane hepatitis, both of which may share pathophysiologic mechanisms. Exposure to HCFC-123 needs to be listed as a potential cause of acute liver failure, and to be considered in patients with acute hepatitis of uncertain etiology and negative viral serology.

Conversion Surgery in Metastatic Gastric Cancer and Cancer Dormancy as a Prognostic Biomarker.

The role of conversion surgery in metastatic gastric cancer remains unclear. Cancer dormancy markers might have a role in predicting the survival in patients with conversion surgery. We identified 26 patients who went through conversion surgery, i.e., a curative-intent gastrectomy with metastasectomy after chemotherapy in initially metastatic gastric cancer. As controls, 114 potential candidates for conversion surgery who only received chemotherapy were included for the propensity score matching. Conversion surgery showed a significantly longer overall survival (OS) compared with only palliative chemotherapy (median-43.6 vs. 14.0 months, respectively, p < 0.001). This better survival in the conversion surgery group persisted even after propensity matching (p < 0.001), and also when compared to patients with tumor response over 5.1 months in the chemotherapy only group (p = 0.005). In the conversion surgery group, OS was longer in patients with R0 resection (22/26, 84.6%) than without R0 resection (4/26, 15.4%) (median-not reached vs 22.1 months, respectively, p = 0.005). Although it should be interpreted with caution due to the primitive analysis in a small population, the positive expression of NR2F1 showed a longer duration of disease-free survival (DFS) after conversion surgery (p = 0.016). In conclusion, conversion surgery showed a durable OS even in patients with initially metastatic gastric cancer when R0 resection was achieved after chemotherapy.

What physicians should know about the management of chronic hepatitis B in children: East side story.

Understanding the natural course of chronic hepatitis B virus (HBV) infection is very important for the management and treatment of chronic hepatitis B in children. Based on treatment guidelines, the management of HBV carriers and treatment of active hepatitis have been advancing and resulted in increased survival, as well as decreased risks of complications such as liver cirrhosis and hepatocellular carcinoma. Development of a continuing medical education (CME) program for primary physicians becomes an important responsibility of pediatric hepatologists. CME could prevent misdiagnosis and unnecessary treatment that could lead to liver complications or antiviral resistance. In addition, education of patients and their parents is necessary to achieve better therapeutic outcomes.