Nationwide Data on the Characteristics of Linked-to-Care Chronic Hepatitis B in Korea.

Linkage-to-care rate of chronic hepatitis B (CHB) is less well characterized. We aimed to evaluate the proportion, characteristics of CHB patients who are linked to care. We retrospectively analyzed insurance reimbursement claims data provided by the Korean National Health Insurance Service. CHB patients who had at least two clinic or hospital visits that were associated with a CHB diagnostic code during 2002-2006 were included. Those without a history of malignancy at baseline were followed up until 2018. Mean follow-up period was 14.5 ± 2.9 years. Among the participants, 553,085 patients (35.8%) were found to be linked to care. The rates were lower in men than women (35.7% vs. 36.0%, p = 0.006). By age, it was highest for the 40's age group at 44.8% and lowest at 29.4% for the 20's age group (All p < 0.0001). The linkage-to-care rate was higher in rural area than metropolitan area (p < 0.0001). The 15-year cumulative incidence of hepatocellular carcinoma and overall survival rates among linked-to-care CHB patients were 18.2% and 93.8%, respectively. Two thirds of CHB patients were not linked to care. Those who are male, dwelling in metropolitan areas, and not in life transition periods need to be targeted to improve the linkage-to-care rate in Korea.

Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis.

AIM: To investigate survival rate and incidence of hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis in the antiviral era. METHODS: We used the Korean Health Insurance Review and Assessment. Korea's health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance guidelines. Overall, 48365 antiviral treatment-naïve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1st decompensated chronic hepatitis B (CHB) and treatment-naïve patients (n = 7166). RESULTS: The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1st decompensated CHB treatment-naïve subjects. But the annual mortality rates sharply decreased to 3.4% (2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5% (1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-naïve patients was 3.4% (2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-naïve patients. CONCLUSION: Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.

Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial.

OBJECTIVE: We aimed to evaluate the effects of carnitine-orotate complex in patients with nonalcoholic fatty liver disease (NAFLD) and diabetes. RESEARCH DESIGN AND METHODS: Eight hospitals in Korea participated in this randomized, controlled, double-blind trial of patients with diabetes and NAFLD. Seventy-eight patients were randomly assigned in a 1:1 ratio to receive carnitine-orotate complex (824 mg, three times daily) or matching placebo. The primary study outcome was decline in alanine aminotransferase (ALT) to the normal range. Secondary study outcomes were change in ALT, radiological hepatic steatosis, parameters for anthropometry, liver function, lipid profiles, and glycemic control. Hepatic steatosis was assessed using Hounsfield units on noncontrast computed tomography (CT) imaging with hepatic attenuation. RESULTS: After 12 weeks of treatment, compared with placebo group, carnitine-orotate complex-treated participants had a significantly higher rate of normalization of serum ALT level (17.9% vs. 89.7%, P < 0.001). On hepatic CT analysis, participants treated with carnitine-orotate complex showed an increased liver attenuation index (0.74 ± 8.05 vs. 6.21 ± 8.96, P < 0.008). A significant decrease in HbA1c was observed in the carnitine-orotate complex group (-0.33 ± 0.82% [-3.6 ± 9.0 mmol/mol], P = 0.007), but no significant change was seen in the placebo group. CONCLUSIONS: Treatment with carnitine-orotate complex improves serum ALT and may improve hepatic steatosis as assessed by CT in patients with diabetes and NAFLD. Further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.

Effect of Color of Light Emitting Diode on Development of Fruit Body in Hypsizygus marmoreus.

This study was conducted to identify a suitable color of light for development of the fruit body in Hypsizygus marmoreus. To accomplish this, samples were irradiated with blue (475 nm), green (525 nm), yellow (590 nm), or red (660 nm) light emitting diodes (LEDs) to induce the formation of fruiting bodies after mycelia growth. The diameter and thickness of the pileus and length of stipes in samples subjected to blue LED treatment were similar to those of subjected to fluorescent light (control), and the lengths of the stipes were highest in response to treatment with the red LED and darkness. The commercial yields of plants subjected to blue and green LED treatment were similar to those of the control. In conclusion, cultivation of H. marmoreus coupled with exposure to blue LED is useful for inducing high quality fruit bodies as well as higher levels of ergosterol, DPPH radical scavenging activity, total polyphenol content and reducing power.

Optimal Conditions for the Mycelial Growth of Coprinus comatus Strains.

The principal objective of this study was to acquire basic data regarding the mycelial growth characteristics for the artificial cultivation of Coprinus comatus. 12 URP primers were employed to evaluate the genetic relationships of C. comatus, and the results were divided into three groups. Among six kinds of mushroom media, MYP medium was selected as the most favorable culture medium for C. comatus. The optimal temperature and pH ranges for the mycelial growth of C. comatus were 23~26℃ and pH 6~8, respectively. The carbon and nitrogen sources for optimal mycelial growth were sucrose and tryptone, respectively.

Determination of the active metabolites of sibutramine in rat serum using column-switching HPLC.

A simple and direct analysis using column-switching HPLC method was developed and validated for the quantification of active metabolites of sibutramine, N-mono-desmethyl metabolite (metabolite 1, M1) and N-di-desmethyl metabolite (metabolite 2, M2) in the serum of rats administered sibutramine HCl (5.0 mg/kg, p.o.). Rat serum was directly injected onto the precolumn without sample prepreparation step following dilution with mobile phase A, i. e., methanol-ACN-20 mM ammonium phosphate buffer (pH 6.0 with phosphoric acid) (8.3:4.5:87.2 by volume). After the endogenous serum components were eluted to waste, the system was switched and the analytes were eluted to the trap column. Active metabolites M1 and M2 were then back-flushed to the analytical column for separation with mobile phase B, i. e., methanol-ACN-20 mM ammonium phosphate buffer (pH 6.0 with phosphoric acid) (35.8:19.2:45 by volume) and detected at 223 nm. The calibration curves of active metabolites M1 and M2 were linear in the range of 0.1-1.0 microg/mL and 0.15-1.8 microg/mL. This method was fully validated and shown to be specific, accurate (10.4-10.7% error), and precise (1.97-8.79% CV). This simple and rapid analytical method using column-switching appears to be useful for the pharmacokinetic study of active metabolites (M1 and M2) of sibutramine.

Augmentation of Ca2+-induced microsomal triglyceride transfer protein activity by glucose supply enhances hypertriglyceridemia in vivo.

We have investigated possible roles of intra-glucose supply on microsomal triglyceride (TG) transfer protein (MTP) in the secretion of TG-rich very low-density lipoprotein (VLDL) from the liver. Due to the activation of MTP, TG and apolipoprotein B (apoB) in the liver are assembled into VLDL and then the VLDL is transferred into the blood stream. High MTP activity can increase the release of VLDL into the blood stream, and this would lead high levels of TG and apoB in the blood. High MTP activity was found when the liver (or hepatocytes) contained a high level of total Ca2+ as a response of glucose administration. However, the MTP activity was reduced in response to the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7, Ki=25 microM), the intracellular Ca2+ chelator BAPTA-AM, and the extracellular Ca2+ chelator EDTA. These suggested that there might be a very close relationship between high MTP activity and high Ca2+ level in the liver by glucose administration. Glucose-derived hyperglycemic condition resulted from those elevations of TG and total cholesterol in the liver. This hyperglycemic phenomenon may be associated with the increase of TG and apoB levels in blood. The possibility for the regulation of VLDL formation in the liver and, further, those related circulatory diseases due to the excess of VLDL in the blood stream by controlling MTP activity in association with Ca2+ was investigated.

The possible role of Ca2+ on the activation of microsomal triglyceride transfer protein in rat hepatocytes.

Microsomal triglyceride (TG) transfer protein (MTP) is involved in the secretion of TG-rich very low-density lipoprotein (VLDL), a process which leads to the generation of hypertriglyceridemia and atherosclerosis. We investigated the possible role of Ca(2+) on MTP activity in hepatocytes. Exogenous CaCl(2) and calmodulin increased MTP activity dose-dependently, and calcium ionophore A23187 (A23187) also increased total Ca(2+) level and MTP activity in hepatocytes. Moreover, MTP activity increased by CaCl(2) or A23187 was abrogated in the presence of EDTA, a Ca(2+) chelator. MTP activity was increased by the simultaneous addition of CaCl(2) and calmodulin. However, this increase was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), a Ca(2+) antagonist. A23187 increased the release of TG and cholesterol from hepatocytes, and these were inhibited by EDTA. A23187 also increased the ratio of TG to HDL-cholesterol in hepatocytes culture medium, which indicates the release of TG is higher than that of HDL-cholesterol from hepatocytes. Thus, our findings demonstrate that hepatocellular Ca(2+) contributes directly or indirectly to MTP activation. In conclusion, the inhibition of MTP activity via the suppression of hepatocellular Ca(2+) may result in the inhibition of hypertriglyceridemia.