NAFLD Is Associated with High Prevalence and High Recurrence Rate in Patients with Breast Cancer

( Young-sun Lee ),( Sung Won Chang ),( Ha Seok Lee ),( Haein Bak ),( Sehwa Kim ),( Min-jin Lee ),( Chan Uk Lee ),( Young Kul Jung ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Jong Eun Yeon 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Breast cancer is most common cancer in women worldwide. The incidence of breast cancer is correlated with metabolic component including diabetes, hypertension, and obesity. Likewise breast cancer, metabolic components are important risk factors for development of NAFLD. In this study, we analyzed the prevalence of NAFLD in patients with breast cancer and the effect of NAFLD on the prognosis of breast cancer. Methods: Patients with breast cancer were enrolled from January 2007 to June 2017. Patients who had other chronic liver were excluded. Hepatic steatosis was evaluated by non-enhanced CT scan. We diagnosed NAFLD when the mean attenuation of the liver is lower than 40 HU or 10 HU lower than that of the spleen. 123 healthy controls who took non-enhanced CT scan were also analyzed. Results: Total 1587 patients were enrolled from January 2007 to June 2017. The prevalence of NAFLD in patients with breast cancer was 15.8% (251/1587) and it was significantly higher comparing with healthy control (8.9%, 11/123)(P=0.036). After propensity score matching, the difference of NAFLD prevalence was still significant between control group (8.9%, 11/123) and breast cancer patients (17.9%, 22/123) (P=0.040). In breast cancer patients, overall survival did not showed significant difference between NAFLD group and non-NAFLD group (P=0.304) (Figure A). However, recurrence-free survival was significantly higher in patients without NAFLD comparing with those with NAFLD (P=0.009) (Figure B). Among breast cancer patients received endocrine treatment, NAFLD group showed higher cumulative incidence of significant liver injury comparing with non-NAFLD group (P<0.001). Conclusions: The prevalence of NAFLD in patients with breast cancer is significantly high compared to healthy control group. Moreover, breast cancer patients with NAFLD showed poor prognosis in terms of recurrence. Therefore, diagnostic evaluation to determine whether or not NAFLD is present would be important in managing patients with breast cancer.

Elevated Biochemical Parameters among Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD) in Nepal

( Narayan Prasad Parajuli ),( Shreena Shakya ),( Jyotsna Shakya ),( Puspa Raj Khanal ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple steatosis, through steatohepatitis to fibrosis and ultimately cirrhosis and hepatocellular carcinoma. Globally, NAFLD is being increasingly recognized as a major health burden. In this study, we aimed to investigate the patients with NAFLD and compare various biochemical parameters among patients with and without NAFLD at a tertiary care teaching hospital of Kathmandu, Nepal. Methods: We conducted a hospital based cross sectional study among 143 (73 NAFLD and 70 control) patients visiting a tertiary care teaching hospital of Nepal for their annual medical checkup. Diagnosis of NAFLD was made by abdominal ultrasonography and liver parameters. Analysis of blood chemistry parameters (lipid profile, liver profile and hematology parameters) in the patients with and without NAFLD (control) was carried out by standard methods. Statistical analysis and comparison of the parameters was done by SPSS version 21.0 and data with p value less than 0.05 was considered significant. Results: Among 73 cases diagnosed as NAFLD, ultrasonography revealed 54.7% of the cases as grade I NAFLD, 32.8% as grade II and remaining 12.5% as grade III NAFLD. Mean age for the patient with NAFLD was 41.6 years with male predominance (38, 52.0%). Among the NAFLD cases, 33(45.2%) patients had normal liver profile in which 18(54.5%) of them had abnormal lipid profile. Subsequently, we observed significantly (p<0.001) high levels of fasting blood glucose, serum uric acid, total cholesterol, triglycerides, LDL cholesterol, serum transaminases (AST-ALT) and alkaline phosphatase among NAFLD group of patients. However, no significant difference was noted on blood levels of urea, creatinine and other hematological parameters. Conclusions: Non-alcoholic fatty liver disease was found associated with abnormal biochemical parameters. Timely detection of the cases and establishment of appropriate control measures will be helpful in modifying the disease course and delaying complications.

Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: Nationwide surveys (KNHANES 2008-2011)

Lee, Y.h.,Jung, K.S.,Kim, S.U.,Yoon, H.j.,Yun, Y.J.,Lee, B.W.,Kang, E.S.,Han, K.H.,Lee, H.C.,Cha, B.S. Elsevier Science Publishers 2015 Journal of hepatology Vol.63 No.2

Background & Aims: Although sarcopaenia is associated with obesity-related comorbidities, its influence on non-alcoholic fatty liver disease (NAFLD) or steatohepatitis has not been fully determined. We aimed to investigate the direct relationship between sarcopaenia and NAFLD or steatohepatitis in the general population. Methods: We conducted a cross-sectional study using nationally representative samples of 15,132 subjects from the Korea National Health and Nutrition Examination Surveys 2008-2011. Subjects were defined as having NAFLD when they had higher scores from previously validated NAFLD prediction models such as the hepatic steatosis index, comprehensive NAFLD score and NAFLD liver fat score. BARD and FIB-4 scores were used to define advanced fibrosis in subjects with NAFLD. The skeletal muscle index (SMI) [SMI(%)=total appendicular skeletal muscle mass (kg)/weight (kg)x100] measured by dual-energy X-ray absorptiometry was used to diagnose sarcopaenia with cut points of 32.2% for men and 25.5% for women. Results: SMI was inversely correlated with all NAFLD predicting scores (Ps<0.001). After stratification, sarcopaenic subjects had an increased risk of NAFLD regardless of obesity (odds ratios [ORs]=1.55 to 3.02, depending on models; all Ps<0.001) or metabolic syndrome (ORs=1.63 to 4.00, all Ps<0.001). Multiple logistic regression analysis also demonstrated this independent association between sarcopaenia and NAFLD after adjusting for confounding factors related to obesity or insulin resistance (ORs=1.18 to 1.22, all Ps<0.001). Furthermore, among the NAFLD population, subjects with lower SMIs were likely to have advanced fibrosis compared with non-sarcopaenic individuals (BARD and FIB-4: ORs=1.83 and 1.69, respectively; both Ps<0.001). Compared with non-exercised subjects, individuals who exercised regularly had a lower risk of NAFLD (p<0.001), particularly among obese people with well-preserved muscle mass. Conclusions: Sarcopaenia is associated with increased risks of NAFLD and advanced fibrosis, independent of obesity or metabolic control.

Hepatic STAMP2 alleviates high fat diet-induced hepatic steatosis and insulin resistance

Kim, H.Y.,Park, S.Y.,Lee, M.H.,Rho, J.H.,Oh, Y.J.,Jung, H.U.,Yoo, S.H.,Jeong, N.Y.,Lee, H.J.,Suh, S.,Seo, S.Y.,Cheong, J.,Jeong, J.S.,Yoo, Y.H. Elsevier Science Publishers 2015 Journal of hepatology Vol.63 No.2

Background & Aims: Most studies on the role of STAMP2 in metabolism have used adipose tissue. Little knowledge exists concerning the role of STAMP2 in the liver, which is a metabolically central target. We hypothesized that STAMP2 is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. Methods: We examined our hypothesis using human NAFLD patient pathology samples and a high-fat diet (HFD)-induced NAFLD mouse model. The molecular mechanism underlying hepatic STAMP2-mediated lipid imbalance was explored using an oleic acid (OA)-induced NAFLD in vitro model. Results: Noticeably, the expression level of STAMP2 protein was reduced in the livers obtained from NAFLD patients and HFD-induced NAFLD mice. In vivo knockdown of hepatic STAMP2 by siRNA accelerated hepatic steatosis and insulin resistance in mice fed a HFD. Conversely, the delivery of adenoviral STAMP2 (Ad-STAMP2) improved hepatic steatosis in HFD-induced NAFLD mice. The expression of lipogenic or adipogenic factors was increased in both in vitro and in vivo NAFLD models but was reversed by Ad-STAMP2. Adenoviral overexpression of STAMP2 improved insulin resistance in the HFD-induced NAFLD mice. In vivo and in vitro assays demonstrated that STAMP2 modulates insulin sensitivity and glucose metabolism and that STAMP2 counteracts OA-induced insulin resistance by modulating insulin receptor substrate-1 stability. Conclusions: The present study revealed that hepatic STAMP2 plays a pivotal role in preventing HFD-induced NAFLD and that STAMP2 overexpression improves hepatic steatosis and insulin resistance in NAFLD. Our findings indicate that STAMP2 may represent a suitable target for interventions targeting NAFLD.

Exosomal miRNA Regulates Liver Fibrosis during Progres-sion of Nonalcoholic Fatty Liver Disease

( Young-sun Lee ),( Eunjung Ko ),( Yang Jae Yoo ),( Jihye Je ),( Sang Jun Suh ),( Young Kul Jung ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Jong Eun Yeon ),( Kwan Soo Byun ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Although nonalcoholic fatty liver disease (NAFLD) is becoming dominant cause of chronic liver disease, the exact mechanism of fibrosis progression in NAFLD have yet to be elucidated. We aimed to investigate the role of exosomal miRNA during fibrosis progression in NAFLD. Methods: We isolated exosomes from supernatant of human hepatoma cell line (Huh7) with or without palmitic acid treatment. Exosomal miRNA profiles were analyzed using a microarray. LX-2 cells, human hepatic stellate cell (HSC) line, were treated with isolated exosome or were transfected with miRNA. Collected LX-2 cells were subjected to real-time PCR for evaluation of fibrosis marker. In addition, we analyzed miRNA expression in exosomes from the sera in biopsy proven NAFLD patients. Results: Compared with controls, PA-treated hepatocytes displayed significantly increased exosome production (8.6 vs. 5.5 X 10^7 /μL, P < 0.001). The microarray data showed distinctive expression levels of miRNA between exosomes from vehicle- and PA-treated hepatocytes. In exosomes from PA-treated hepatocyte, the expression of miRNA 122 and 192 were significantly increased compared with controls. When LX-2 cells were cultured with exosomes from PA-treated hepatocytes, expression of fibrosis markers (TGF-β 1, α-SMA, and Col1a1) in LX-2 cells increased compared to those from vehicle-treated hepatocytes. When we transfected HSCs with miRNA 192, it showed enhanced expression of fibrosis markers comparing with negative control. In accordance with in vitro, the number of exosomes significantly increased in sera from advanced stage NAFLD patients compared to early stage NAFLD patients (21.73 vs. 9.75 X 10⁷/μL, P < 0.001). Also, miRNA 122 and 192 expression were significantly increased in sera from advanced stage NAFLD patients compared to early stage NAFLD patients (21.73 vs. 9.75 X 10⁷/μl, P < 0.001). Conclusions: PA treatment accelerated the production of exosomes in hepatocytes and altered their miRNA profile. Advanced stage NAFLD patients showed distinct number of exosomes and expression of miRNA in exosomes from sera compared to early stage NAFLD patients. Direct transfection of miRNA 192 into HSCs increased the expression of fibrosis marker genes in HSCs. Therefore, exosomes and exosomal miRNA might have important roles for crosstalk between hepatocytes and HSCs in the fibrosis progression in NAFLD.

유산소 운동 강도가 아동기 비만 쥐의 비알코올성 지방간 완화에 미치는 영향

배주용,고강은,이율효 한국융합과학회 2022 한국융합과학회지 Vol.11 No.6

Purpose Most studies on nonalcoholic fatty liver disease (NAFLD) focused on the subject in middle-aged or elderly adults. However, the negative effects of temporary high-fat diet may differ according to age, and the effective intensity of exercise for alleviation of NAFLD may also differ according to age. The purpose of this study was to examine the changes in hepatic steatosis caused by temporary high-fat diet and to analyze the effect of aerobic exercise intensity on NAFLD in young-aged mice. Methods 4 weeks old male C57BL/6 mice were classified into a normal diet group (CO, n = 8) or a high-fat diet group (HF, n = 24). HF group consumed a high-fat diet for 8 weeks. After then, HF group was randomly assigned to the HF+non-exercise group (HF, n = 8), HF+low-intensity aerobic exercise group (HFLE, n = 8), and HF+high-intensity aerobic exercise group (HFHE, n = 8). The mice in the exercise group conducted aerobic exercise 5 times a week for 8 weeks at their exercise intensity. Results After 8 weeks of high-fat diet, body weight, liver weight, liver TG, and liver lipid droplets in the HF group were significantly increased. However, although fat synthesis-related factors were still high, regular exercise was effective in relieving fatty liver by increasing carnitine palmitoyl transferase-1 and phospho AMP-activated protein kinase proteins. In addition, high-intensity aerobic exercise effectively reduced liver TG and lipid droplets compared to low-intensity aerobic exercise. Conclusion High-intensity aerobic exercise was more effective in alleviating NAFLD than low-intensity exercise by decreasing the liver weight and liver TG. Therefore, high-intensity exercise can be recommended as an effective exercise for alleviating NAFLD in childhood. 연구목적 NAFLD에 관한 대부분의 연구는 중년 또는 노년 등의 성인에게 초점을 맞추고 있다. 하지만 일시적인 고지방 식이섭취로 인한 부정적인 효과는 연령에 따라 다르게 나타날 수 있으며, 또한 NAFLD를 완화하기 위한 효과적인 운동 강도 역시 연령에 따라 다를 수 있다. 본 연구에서는 아동기 쥐의 일시적인 고지방 식이 섭취로 인한 간 지방증의 변화를 살펴보고, 유산소 운동 강도가 NAFLD에 미치는 영향을 분석하고자 하였다. 연구방법 4주령의 수컷 C57BL/6 쥐를 분양받아, 일반식이 섭취군 (CO, n = 8)과 고지방식이 섭취군 (HF, n = 24)으로 분류하였다. HF군은 8주간의 고지방 식이를 섭취하였으며, 그 후, HF군의 쥐들은 무작위로 HF+비운동군(HF, n = 8), HF+저강도 유산소운동군(HFLE, n = 8), 그리고 HF+고강도 유산소운동군(HFHE, n = 8)으로 분류하였다. 운동군의 쥐들은 자신의 운동강도로 8주간 주 5회의 유산소 운동을 실시하였다. 결과 고지방식이 8주 후 HF 그룹의 체중, 간 무게, 간 TG 및 간 지방 방울이 유의하게 증가했다. 그러나 규칙적인 운동은 지방합성 관련인자를 유의하게 증가시켰지만, carnitine palmitoyl transferase-1과 phospho AMP-activated protein kinase 단백질을 증가시킴으로써, 지방간 완화에 효과적인 것으로 나타났다. 또한, 고강도 운동은 저강도 운동에 비해 간 TG 및 지방 방울 감소에 효과적인 것으로 나타났다. 결론 고강도 유산소 운동은 저강도 운동보다 간의 무게와 간 TG를 현저하게 감소시킴으로써 NAFLD 완화에 더 효과적이었다. 따라서 아동기에 NAFLD를 완화시키는 효과적인 운동으로 고강도 운동을 권장할 수 있음을 제안한다.

Effect of Non-Alcoholic Fatty Liver Disease on Components of Metabolic Syndrome in Post-menopausal Women

Moon-Jung Shim,Jee-Aee Im 대한의생명과학회 2008 Biomedical Science Letters Vol.14 No.4

Non-alcoholic fatty liver disease (NAFLD) is associated with various metabolic abnormalities, including central obesity, type 2 diabetes, dyslipidemia, and high blood pressure. This suggests that NAFLD may represent the hepatic manifestation of the metabolic syndrome. In this study, we investigated unfavorable effects NAFLD on components of metabolic syndrome in post-menopause women. Eight hundred sixty-nine postmenopausal women were recruited for this study. The diagnosis of fatty liver was based on the results of abdominal ultrasonography. Serum levels of fasting glucose, total cholesterol, triglyceride, and HDL-cholesterol were measured. The prevalence of component of metabolic syndrome such as hypertension, hyperglycemia, hypertriglyceridemia, and low-HDL-cholesterol was significantly higher in subjects with NAFLD as compared with those without NAFLD. The moderate to severe grade of NAFLD presented higher levels of serum fasting glucose, fasting insulin, HOMA-IR, total cholesterol, and triglycerides than the mild NAFLD and the normal group. In conclusion, metabolic syndrome risk was increased in post-menopause women with NAFLD as compared with those without NAFLD. The severity of NAFLD affected metabolic syndrome risk factors. The optimal strategy for the treatment of NAFLD is likely to include lifestyle modifications and therapy to improve insulin resistance.

Effect of Non-Alcoholic Fatty Liver Disease on Components of Metabolic Syndrome in Post-menopausal Women

Shim, Moon-Jung,Im, Jee-Aee The Korean Society for Biomedical Laboratory Scien 2008 Journal of biomedical laboratory sciences Vol.14 No.4

Non-alcoholic fatty liver disease (NAFLD) is associated with various metabolic abnormalities, including central obesity, type 2 diabetes, dyslipidemia, and high blood pressure. This suggests that NAFLD may represent the hepatic manifestation of the metabolic syndrome. In this study, we investigated unfavorable effects NAFLD on components of metabolic syndrome in post-menopause women. Eight hundred sixty-nine postmenopausal women were recruited for this study. The diagnosis of fatty liver was based on the results of abdominal ultrasonography. Serum levels of fasting glucose, total cholesterol, triglyceride, and HDL-cholesterol were measured. The prevalence of component of metabolic syndrome such as hypertension, hyperglycemia, hypertriglyceridemia, and low-HDL-cholesterol was significantly higher in subjects with NAFLD as compared with those without NAFLD. The moderate to severe grade of NAFLD presented higher levels of serum fasting glucose, fasting insulin, HOMA-IR, total cholesterol, and triglycerides than the mild NAFLD and the normal group. In conclusion, metabolic syndrome risk was increased in post-menopause women with NAFLD as compared with those without NAFLD. The severity of NAFLD affected metabolic syndrome risk factors. The optimal strategy for the treatment of NAFLD is likely to include lifestyle modifications and therapy to improve insulin resistance.

Exercise-mediated macrophage polarization modulates the targeted therapeutic effect of NAFLD: a review

Li Zhenyu,Wang Ying,Tian Zhuang,Xie Yongchao,김재철 한국운동영양학회 2023 Physical Activity and Nutrition (Phys Act Nutr) Vol.27 No.3

[Purpose] This review aims to explore the exercise-mediated hepatic macrophage polarization mechanism and its effect on improving and regulating non-alcoholic fatty liver disease (NAFLD) by analyzing the pathogenesis of NAFLD and the cause of the influence of hepatic macrophage polarization. In addition to exploring the varied effects of different exercise types on macrophage polarization regulation in NAFLD, to provide a direction and basis for the treatment of NA- FLD. [Methods] The research methodology involved a comprehensive search of the PubMed database using specific keywords such as “NAFLD”, “macrophage polarization”, and “exercise”, to retrieve relevant literature published. [Results] (1) The main factors inducing NAFLD were high-fat diet, obesity, insulin resistance (IR), changes in gut microbiota, and genetic variation in susceptibility. (2) Drug treatment, nutrient induction, microfactor induction, physiological environment induction, and other factors can induce the polarization of hepatic macrophages and affect NAFLD. (3) Different intensities, types, and frequencies of exercise have different effects on polarization macrophages, and may also differently effects improving liver inflammation, fibrosis, and NAFLD. Curently, regular moderate-intensity aerobic exercise is the most effective therapy for treating NAFLD. [Conclusion] Approaches to ameliorate NAFLD with exercise involve strategies to alter macrophage polarization by inhibiting M1 or driving M2 activation. However, research on the different types of exercise-mediated macrophage polarization mechanisms and differences in therapeutic effects is not yet sufficient. Future research is necessary to explore the exact mechanisms and differences in the effects of different exercises on the treatment of NAFLD.

Clinical Impact of Hepatic Steatosis in Patients with Chronic Hepatitis B Infection on Tenofovir Therapy

( Jeong Eun Song ),( Young Eun Cheon ),( Hye Won Lee ),( Beom Kyung Kim ),( Seung Up Kim ),( Do Young Kim ),( Sang Hoon Ahn ),( Seong Gyu Hwang ),( Kwang-hyub Han ),( Jun Yong Park ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: To further observe and identify the effect of nonalcoholic fatty liver disease (NAFLD) on the response to tenofovir disoproxil fumarate (TDF) treatment in patients with chronic hepatitis B (CHB). Methods: From 2012-2014, consecutive antiviral-naïve CHB patients who started TDF and underwent controlled attenuated parameter (CAP) measurement were enrolled from two tertiary medical center. Based on CAP score, patients were divided into groups with NAFLD (CAP score ≥ 250) and non-NALFD (CAP score < 250). The demographic, anthropometric and clinical data was investigated at baseline, 24wk, 48wk, and 96wk. Results: A total of 159 patients (mean age 47.23±11.61 years, 90 (56.6%) males) were involved in the study, with overall percentages of NAFLD as 35.8% (n=57). The two groups were not significantly different in terms of age, sex, biochemical parameters and the status of compensated liver cirrhosis. Moreover, HBV DNA level and the status of HBeAg positive were equally distributed in both two groups. However, the NAFLD group showed a higher level of BMI compared with non-NAFLD group (p < 0.05). Although the HBV DNA undetectable rate increased gradually after treatment with TDF in both two groups, non-NAFLD group showed a higher virological response rate compared to NAFLD group (54.4% vs. 41.1%, 80.6% vs. 69.6%, 95% vs. 72.7%; week 24, week 48, week 96, respectively). However, there was significant difference between two groups only at week 96 (p<0.001). The rate of ALT normalization was higher in non-NAFLD group throughout the whole time spot, but reached no statistical significance. Multivariate analysis indicated that a higher HBV DNA level was associated with early virological non-response and that hepatic steatosis may influence long-term virological non-response. Conclusions: NAFLD significantly affected long-term virological response in CHB patients treated with TDF. Further investigation is needed in the future, which calls for a specific antiviral strategy in CHB patients with NAFLD.