Fibrotic Burden in the Liver Differs Across Metabolic Dysfunction-Associated Fatty Liver Disease Subtypes

Background/Aims@#Metabolic dysfunction-associated fatty liver disease (MAFLD) is categorized into three subtypes: overweight/obese (OW), leanormal weight with metabolic abnormalities, and diabetes mellitus (DM). We investigated whether fibrotic burden in liver differs across subtypes of MAFLD patients. @*Methods@#This cross-sectional multicenter study was done in cohorts of subjects who underwent a comprehensive medical health checkup between January 2014 and December 2020. A total of 42,651 patients with ultrasound-diagnosed fatty liver were included. Patients were classified as no MAFLD, OW-MAFLD, lean-MAFLD, and DM-MAFLD. Advanced liver fibrosis was defined based on the nonalcoholic fatty liver disease fibrosis score (NFS) or fibrosis-4 (FIB-4) index. @*Results@#The mean age of the patients was 50.0 years, and 74.1% were male. The proportion of patients with NFS-defined advanced liver fibrosis was the highest in DM-MAFLD (6.6%), followed by OW-MAFLD (2.0%), lean-MAFLD (1.3%), and no MAFLD (0.2%). The proportion of patients with FIB-4-defined advanced liver fibrosis was the highest in DM-MAFLD (8.6%), followed by lean-MAFLD (3.9%), OW-MAFLD (3.0%), and no MAFLD (2.0%). With the no MAFLD group as reference, the adjusted odds ratios (95% confidence intervals) for NFS-defined advanced liver fibrosis were 4.46 (2.09 to 9.51), 2.81 (1.12 to 6.39), and 9.52 (4.46 to 20.36) in OW-MAFLD, leanMAFLD, and DM-MAFLD, respectively, and the adjusted odds ratios for FIB-4-defined advanced liver fibrosis were 1.03 (0.78 to 1.36), 1.14 (0.82 to 1.57), and 1.97 (1.48 to 2.62) in OW-MAFLD, lean-MAFLD, and DM-MAFLD. @*Conclusions@#Fibrotic burden in the liver differs across MAFLD subtypes. Optimized surveillance strategies and therapeutic options might be needed for different MAFLD subtypes.

Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Background/Aims@#Posthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model. @*Methods@#A total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model. @*Results@#PHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (≤3.8 g/dL; OR 15.89, 95% CI 2.41 to 104.82, p=0.004), major hepatic resection (OR 4.16, 95% CI 1.40 to 12.38, p=0.014), higher albumin-bilirubin score (>–0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum α-fetoprotein (>100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF. @*Conclusions@#Our novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF.

Infiltrative hepatocellular carcinoma with multiple lung metastasis completely cured using nivolumab: a case report

The current Food and Drug Administration-approved systemic treatments for advanced hepatocellular carcinoma (HCC) include multikinase inhibitors (tyrosine kinase inhibitor [TKI]) and immune checkpoint inhibitors (ICIs). Among ICIs, nivolumab is used as secondline therapy for advanced HCC after sorafenib failure or patient intolerance. In this case, a patient with infiltrative HCC and portal vein tumor thrombosis was treated with hepatic arterial infusion chemotherapy (HAIC) and radiation therapy. New lung metastasis developed after HAICs; thus, lenvatinib treatment was initiated. However, the disease progressed. Thereafter, sorafenib treatment was initiated but he developed intolerance, with grade 3 sorafenib-related diarrhea. Subsequently, nivolumab was administered as rescue therapy. He demonstrated a partial response to nivolumab after the third treatment and viable HCCs in the lungs and liver completely disappeared after the 24th treatment. These findings suggest that nivolumab could be used as an effective rescue therapy for advanced HCC progression after TKI treatment.

Independent Risk Factors for Hepatocellular Carcinoma Recurrence after Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C

Background/Aims@#This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. @*Methods@#A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. @*Results@#Among the 100 patients, 88% achieved a sustained virological response (SVR) 12weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively). @*Conclusions@#DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy.

Infiltrative hepatocellular carcinoma with multiple lung metastasis completely cured using nivolumab: a case report

The current Food and Drug Administration-approved systemic treatments for advanced hepatocellular carcinoma (HCC) include multikinase inhibitors (tyrosine kinase inhibitor [TKI]) and immune checkpoint inhibitors (ICIs). Among ICIs, nivolumab is used as secondline therapy for advanced HCC after sorafenib failure or patient intolerance. In this case, a patient with infiltrative HCC and portal vein tumor thrombosis was treated with hepatic arterial infusion chemotherapy (HAIC) and radiation therapy. New lung metastasis developed after HAICs; thus, lenvatinib treatment was initiated. However, the disease progressed. Thereafter, sorafenib treatment was initiated but he developed intolerance, with grade 3 sorafenib-related diarrhea. Subsequently, nivolumab was administered as rescue therapy. He demonstrated a partial response to nivolumab after the third treatment and viable HCCs in the lungs and liver completely disappeared after the 24th treatment. These findings suggest that nivolumab could be used as an effective rescue therapy for advanced HCC progression after TKI treatment.

Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma

Purpose@#Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. @*Materials and Methods@#Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. @*Results@#Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). @*Conclusion@#High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Independent Risk Factors for Hepatocellular Carcinoma Recurrence after Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C

Background/Aims@#This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. @*Methods@#A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. @*Results@#Among the 100 patients, 88% achieved a sustained virological response (SVR) 12weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively). @*Conclusions@#DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy.

Effect of PTEN Polymorphism on the Development of Hepatitis B Virus-associated Hepatocellular Carcinoma

BACKGROUND/AIMS: Phosphatase and tensin homolog (PTEN) is a known tumor suppressor gene that is downregulated in hepatocellular carcinoma (HCC). Here, we investigated the association between single nucleotide polymorphisms (SNPs) of PTEN and HCC development in patients with hepatitis B virus (HBV) infection. METHODS: Six SNPs of PTEN at positions rs1234221, rs1903860, rs1234220, rs1903858, rs2299941, and rs17431184 were analyzed in a development population (417 chronic HBV carriers without HCC and 281 chronic HBV carriers with HCC). PTEN rs1903858, rs1903860, and rs2299941 SNPs were further assessed for the development of HCC in a validation population of 200 patients with HBV-related liver cirrhosis. RESULTS: In the development population, PTEN rs1903860 C allele, rs1903858 G allele, and rs2299941 G allele were associated with a low risk of HCC. The haplotype A-T-A-A-A was associated with an increased risk of HCC (recessive model; odds ratio=2.277, 95% confidence interval [CI] =1.144-4.532, P=0.019). In the validation population, PTEN rs2299941 G allele was the only significant protective genetic polymorphism related to HCC development after adjustment for age and sex (hazard ratio=0.582, 95% CI =0.353–0.962, P=0.035). CONCLUSIONS: These findings suggest that genetic polymorphisms in PTEN may affect HCC development in patients with chronic HBV infection.

A Proposal for Modification of the Barcelona Clinic Liver Cancer Staging System Considering the Prognostic Implication of Performance Status

BACKGROUND/AIMS: Barcelona Clinic Liver Cancer (BCLC) C stage demonstrates considerable heterogeneity because it includes patients with either symptomatic tumors (performance status [PS], 1–2) or with an invasive tumoral pattern reflected by the presence of vascular invasion (VI) or extrahepatic spread (EHS). This study aimed to derive a more relevant staging system by modification of the BCLC system considering the prognostic implication of PS. METHODS: A total of 7,501 subjects who were registered in the Korean multicenter hepatocellular carcinoma (HCC) registry database from 2008 to 2013 were analyzed. The relative goodness-of-fit between staging systems was compared using the Akaike information criterion (AIC) and integrated area under the curve (IAUC). Three modified BCLC (m-BCLC) systems (#1, #2, and #3) were devised by reducing the role of PS. RESULTS: As a result, the BCLC C stage, which includes patients with PS 1–2 without VI/EHS, was reassigned to stage 0, A, or B according to their tumor burden in the m-BCLC #2 model. This model was identified as the most explanatory and desirable model for HCC staging by demonstrating the smallest AIC (AIC=70,088.01) and the largest IAUC (IAUC=0.722), while the original BCLC showed the largest AIC (AIC=70,697.17) and the smallest IAUC (IAUC=0.705). The m-BCLC #2 stage C was further subclassified into C1, C2, C3, and C4 according to the Child-Pugh score, PS, presence of EHS, and tumor extent. The C1 to C4 subgroups showed significantly different overall survival distribution between groups (p<0.001). CONCLUSIONS: An accurate and relevant staging system for patients with HCC was derived though modification of the BCLC system based on PS.

Improvement of Nonalcoholic Fatty Liver Disease Reduces the Risk of Type 2 Diabetes Mellitus

BACKGROUND/AIMS: Little evidence is available about the effect of change in nonalcoholic fatty liver disease (NAFLD) status on risk of diabetes mellitus (DM) development. In this study, we tried to analyze the DM risk according to change in NAFLD status over time. METHODS: Among a total of 10,141 individuals for whom routine healthcare assessment was performed, 2,726 subjects were selected according to the inclusion/exclusion criteria. NAFLD status change was determined by using serial abdominal ultrasonography and fatty liver index (FLI) during the follow-up period. RESULTS: Subjects were categorized according to change in NAFLD status as follows: 670 subjects in the persistent NAFLD group, 155 subjects in the resolved NAFLD group, 498 subjects in the incident NAFLD group, and 1,403 subjects in the no NAFLD group. Multivariate Cox regression analysis revealed that incident NAFLD (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.08 to 3.50; p=0.026) and persistent NAFLD (HR, 3.59; 95% CI, 2.05 to 6.27; p<0.001) were independent risk factors for predicting DM development, whereas the risk with resolved NAFLD was not significantly different from that with no NAFLD. FLI could reproduce the results acquired by ultrasonography. CONCLUSIONS: This study demonstrated that future DM risk could be influenced by changes in NAFLD status over time. Resolution of NAFLD could reduce the risk of future DM development, while the development of new NAFLD could increase the risk of DM development.

Plasma MicroRNA-21, 26a, and 29a-3p as Predictive Markers for Treatment Response Following Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma

BACKGROUND: We investigated an association between the levels of plasma microRNA (miRNA)-21,

Prediction of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Using 4-Hour Post-Endoscopic Retrograde Cholangiopancreatography Serum Amylase and Lipase Levels

Early post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prediction may allow safe same-day outpatients discharge after ERCP and earlier proper management. This study aimed to assess the usefulness of the 4-hour post-ERCP serum amylase and lipase levels for PEP early prediction and to investigate predictive cut-off values for 4-hour post-ERCP serum amylase and lipase levels for safe discharge and urgent initiation of resuscitation. The data of 516 consecutive patients with native papilla who underwent ERCP between January 2013 and August 2014 were retrospectively reviewed. Serum amylase and lipase levels were measured before, and 4 and 24 hours after ERCP. PEP occurred in 16 (3.1%) patients. The receiver-operator characteristic curve for 4-hour post-ERCP serum amylase and lipase levels showed that the areas under the curve were 0.919 and 0.933, respectively, demonstrating good test performances as predictors for PEP (both P values 1.5 × the upper limit of reference (ULR) was found useful for PEP exclusion with a sensitivity of 93.8%, while 4 × ULR was found useful to guide preventive therapy with the best specificity of 93.2%. Similarly, the lipase level 2 × ULR showed best sensitivity, while 8 × ULR had the best specificity. Logistic regression analysis showed that 4-hour post-ERCP amylase level > 4 × ULR, lipase level > 8 × ULR, precut sphincterotomy, and pancreatic sphincterotomy were significant predictors for PEP. In conclusion, 4-hour post-ERCP amylase and lipase levels are useful early predictors of PEP that can ensure safe discharge or prompt resuscitation after ERCP.

Serum transferrin as a liver fibrosis biomarker in patients with chronic hepatitis B

BACKGROUND/AIMS: Transferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B. METHODS: The study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared. RESULTS: Univariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B. CONCLUSIONS: Serum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.

Clinical Characteristics of Angioedema With Eosinophilia

Angioedema with eosinophilia (AE) is a very rare allergy disease, case reports of which have been published sporadically since 1984. Here, we retrospectively analyzed the clinical features of 10 AE patients in Korea. Nine of the 10 subjects were young females, ranging from 23 to 38 years old. Twenty percent of the subjects had episodic-type AE with high serum IgM and eosinophil counts, while 80% were non-episodic type with normal serum IgM levels but high eosinophil counts. All patients had used systemic corticosteroids to control AE. One patient with refractory episodic-type AE was treated with anti-IgE antibody. This is the first study to evaluate the clinical characteristics of AE in a Korean population.

Clinical Characteristics of Angioedema With Eosinophilia

Angioedema with eosinophilia (AE) is a very rare allergy disease, case reports of which have been published sporadically since 1984. Here, we retrospectively analyzed the clinical features of 10 AE patients in Korea. Nine of the 10 subjects were young females, ranging from 23 to 38 years old. Twenty percent of the subjects had episodic-type AE with high serum IgM and eosinophil counts, while 80% were non-episodic type with normal serum IgM levels but high eosinophil counts. All patients had used systemic corticosteroids to control AE. One patient with refractory episodic-type AE was treated with anti-IgE antibody. This is the first study to evaluate the clinical characteristics of AE in a Korean population.

Association between apolipoprotein E genotype, chronic liver disease, and hepatitis B virus

BACKGROUND/AIMS: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. METHODS: This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. RESULTS: The epsilon3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the epsilon2, epsilon3, and epsilon4 alleles, respectively. Significantly more of those patients carrying the epsilon3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. CONCLUSIONS: The ApoE epsilon3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.

Plasma Choline Concentration of Some Korean Young Adults and Correlation with Dietary Choline Intake

The purpose of this study is to investigate the concentration of plasma choline of Korean and to clarify the relationship between plasma choline concentration and choline intake. Plasma choline concentration of 30 young adults (15 males, 15 females) aged 20 - 30 years living in Deajeon metropolitan city are analyzed and their dietary choline intake. Choline content of one day meal was directly analyzed with the use of enzymatic method. Plasma choline concentration from more than 12 hr fasting blood was analyzed by using HPLC-MS. Choline intakes of male subjects were in the range of 253.51 - 1724.14 mg and those of female subjects were in the range of 240.85 - 938.06 mg. Mean intakes of choline were 634.53+/-353.68 mg in male subjects and 473.99+/-183.76 mg in female subjects. Plasma choline concentration of total subjects was in the range of 5.08 - 14.01 micro mol/L. Mean plasma choline concentration was 9.19+/-2.05 micro mol/L in male subjects and 8.11+/-1.70 micro mol/L in female subjects. Plasma choline concentration did not show significant correlation with choline intake in male and total subjects, but showed positive correlation with choline intake in female subjects (p<0.05). This result shows that more studies on large scaled samples are needed.

Dietary Choline Intake of Korean Young Aldults

This study was conducted to investigate the choline intake of Korean adults for the purpose of preparing a basal data required for the establishment of choline adequate intake (AI). The subjects of 56 Korean young adults were recruited from college students of 20 to 30 years old in Daejeon city. The aliquots of foods that the subjects ate for one day were collected with use of duplicate food collection method and choline content of one day meal directly was analyzed with the use of enzymatic method. Choline intakes of male subjects were in the range of 353.5 ~ 1222.5 mg and those of female subjects were in the range of 213.1 ~ 722.3 mg. Mean intakes of choline were 658.2 +/- 243.9 mg/day in male subjects and 423.3 +/- 133.6 mg/day in female, therefore choline intake of men was about 200mg higher than that of women. Median value in total subjects was 496 mg, male's median was 608.8 mg, female's median was 419.9 mg. When the subjects were devided into 4 groups by choline intake, as less than 75%, 75 ~ 100%, 100 ~ 125% and over 125% based on choline AI of USA (males: 550 mg, females: 425 mg), there was no significant difference between men (64.3%) and wemen (67.9%) in the distribution of the subjects whose choline intake is under the range of 75 ~ 125% AI of USA. However, 10.7% of men and 21.4% of female had choline intake less than 75% AI of USA while the cases of choline intake higher than 125% AI were 25% in male and 10.7% in female. Thus, it is assumed that female case in choline-deficient state would be two times more than male. When adjusted by body weight, choline intake was 9.5 +/- 3.4 mg/kg in men, 8.1 +/- 3.1 mg/kg in women and 8.8 +/- 3.3 mg/kg in total subjects. And choline intake per 1,000 kcal of men, women and total subjects were 277.1 +/- 78.4 mg, 275.9 +/- 62.1 mg and 276.5 +/- 70.1 mg respectively. From these results, it is suggested that these levels of 276.5 +/- 70.1 mg/ 1,000 kcal or 8.8 +/- 3.3 mg/kg B.W. can be used as a reference value for the establishment of AI of choline for Korean, because overall choline intake of these subjects was not in lower state compared to other nutrients intakes obtained from calculation of the food the subjects had taken.