• Journal of Yeungnam Medical Science
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• v.36 no.2
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• pp.67-77
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• 2019

The paradigm of chronic liver diseases has been shifting. Although hepatitis B and C viral infections are still the main causes of liver cirrhosis and hepatocellular carcinoma (HCC), the introduction of effective antiviral drugs may control or cure them in the near future. In contrast, the burden of nonalcoholic fatty liver disease (NAFLD) has been increasing for decades, and 25 to 30% of the general population in Korea is estimated to have NAFLD. Over 10% of NAFLD patients may have nonalcoholic steatohepatitis (NASH), a severe form of NAFLD. NASH can progress to cirrhosis and HCC. NASH is currently the second leading cause to be placed on the liver transplantation list in the United States. NAFLD is associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome. The pathophysiology is complex and associated with lipotoxicity, inflammatory cytokines, apoptosis, and insulin resistance. The only proven effective treatment is weight reduction by diet and exercise. However, this may not be effective for advanced fibrosis or cirrhosis. Therefore, effective drugs are urgently needed for treating these conditions. Unfortunately, no drugs have been approved for the treatment of NASH. Many pharmaceutical companies are trying to develop new drugs for the treatment of NASH. Some of them are in phase 2 or 3 clinical trials. Here, pharmacologic therapies in clinical trials, as well as the basic principles of drug therapy, will be reviewed, focusing on pathophysiology.

• The Journal of Korean Medicine
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• v.32 no.3
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• pp.44-49
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• 2011

Objective: This study aimed to get information on the current status of therapies to date for non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). Methods: All randomized clinical controlled trial (RCT)-derived papers for NAFLD or NASH were reviewed via PubMed Database. Results: 39 RCTs met the review criteria, of which 15 and 24 papers were for NAFLD and NASH, respectively. 83% of the papers were released since 2006, and 30 studies were conducted for western medicines, antioxidants and lifestyle intervention whereas nine trials were done using herbal medicine or acupuncture which showed positive outcome. Conclusions: NAFLD and NASH are new epidemic disorders which can be a target of traditional Oriental medicine. This study will be helpful for the Oriental medicine-based strategies or therapeutic development for them.

• Clinical and Experimental Pediatrics
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• v.56 no.2
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• pp.45-51
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• 2013

Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD) are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.

• Clinical and Experimental Pediatrics
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• v.56 no.1
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• pp.19-25
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• 2013

Purpose: Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD), and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. Methods: This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. Results: Factors associated with hepatic fibrosis (stiffness measurement >5.9 kPa Fibroscan) were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (>5.9 kPa). In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875) presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. Conclusion: APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.

• Journal of Korean Medicine for Obesity Research
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• v.9 no.1
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• pp.79-86
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• 2009

Objectives The purpose of this study was to investigate the clinical effect of oriental obesity therapy on obese patient with non-alcoholic fatty liver disease(NAFLD). Methods The patient was treated from November 17, 2008 to May 15, 2009 for obesity treatment. And the patient had intensive care through admission treatment from November 17, 2008 to November 29, 2008. Electrolipolysis, auricular acupuncture, herbal medicine, low calorie diet and aerobic exercise were done during the treatment period. Results His body Weight decreased from 102.8kg to 82.7kg. The BMI decreased from 35.2kg/m$^2$ to 28.9kg/m$^2$. NAFLD effectively improved on sonography form grade II${\sim}$III to grade I${\sim}$II after oriental obesity therapy, AST decreased from 65 to 19. ALT decreased from 152 to 18. Oriental obesity therapy could be effective to treat obese patient with NAFLD. Conclusions The obese patient with NAFLD improved on sonography by oriental obesity therapy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.3
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• pp.199-206
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• 2016

Purpose: To analyze the associations among the degrees of nonalcoholic fatty liver disease (NAFLD) by ultrasonography and metabolic syndrome, degrees of obesity in children, and degrees of parental obesity. Methods: A total of 198 children with obesity who visited a pediatric obesity clinic were prospectively enrolled in this study. The severity of NAFLD based on ultrasonography was classified into no, mild, moderate, or severe NAFLD group. The degree of obesity based on the percentage over standard weight for height per sex was classified into mild, moderate, or severe. Results: Of 132 patients evaluated for the degree of NAFLD and metabolic syndrome, the p-value of correlation between the two factors was 0.009. Therefore, metabolic syndrome might significantly affect the degree of NAFLD. Of 158 patients evaluated for the degree of NAFLD and the degree of obesity, the p-value of correlation between the two factors was 0.122. Of 154 patients evaluated for the degree of obesity and father's obesity, the p-value was 0.076. Of 159 patients evaluated for the degree of obesity and mother's obesity, the p-value was 0.000, indicating that mother's obesity could significantly affect the degree of obesity in children. Of 142 patients evaluated for the degree of obesity and metabolic syndrome, the p-value was 0.288. Conclusion: Metabolic syndrome might significantly affect the degree of nonalcoholic fatty liver in children. In addition, mother's obesity might be a significant factor that affects the degree of obesity in children.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.109-120
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• 2011

Objectives: The aim of this investigation was to evaluate the efficacy of KHchunggan-tang aqueous extract on the experimental nonalcoholic fatty liver disease(NAFLD) induced by palmitate. Materials and Methods: To generate a cellular model of NAFLD, we used HepG2 cells, a human hepatoma cell line, treated with 0.5 mM palmitate. By this cellular model, effects of KHchunggan-tang aqueous extract were evaluated. Intracellular lipid accumulation, free radical formation, and apoptosis were detected by Nile red staining, 2',7'-dichloroflourescin diacetate(H2DCF-DA), and 4',6-diamidino-2-phenylindole(DAPI)/propidium iodide(PI) staining, respectively. Some proteins related with NAFLD were determined by western blot. Results: Typical pathological features of NAFLD occurred in the cellular model. Palmitate increased the levels of intracellular lipid vacuoles, decreased cell viability, and increased apoptosis. Palmitate increased free radical formation and lipid peroxidation, too. However, KHchunggan-tang aqueous extract reduced palmitate-induced pathologic features, i.e. steatosis, free radical formation, and apoptosis. In addition, KHchunggan-tang aqueous extract suppressed palmitate-activated c-Jun N-terminal kinase(JNK) signaling, and SP600125, a JNK inhibitor, significantly reversed the palmitate-induced pathologic changes as KHchunggan-tang aqueous extract. It means that the signaling pathway other than JNK can be involved in the KHchunggan-tang mediated cellular protection of palmitate-treated Hep G2 cells. Conclusions: These results suggest that KHchunggan-tang aqueous extract has hepatoprotective effects on NAFLD with combined properties in cellular steatosis, ROS production, and cytoprotection, and thus may have valuable clinical applications for treatment of this chronic liver disease.

• Journal of Preventive Medicine and Public Health
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• v.53 no.5
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• pp.342-352
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• 2020

Objectives: The aim of this retrospective cohort study was to investigate whether non-alcoholic fatty liver disease (NAFLD) was associated with incident bone mineral density (BMD) decrease. Methods: This study included 4536 subjects with normal BMD at baseline. NAFLD was defined as the presence of fatty liver on abdominal ultrasonography without significant alcohol consumption or other causes. Decreased BMD was defined as a diagnosis of osteopenia, osteoporosis, or BMD below the expected range for the patient's age based on dual-energy X-ray absorptiometry. Cox proportional hazards models were used to estimate the hazard ratio of incident BMD decrease in subjects with or without NAFLD. Subgroup analyses were conducted according to the relevant factors. Results: Across 13 354 person-years of total follow-up, decreased BMD was observed in 606 subjects, corresponding to an incidence of 45.4 cases per 1000 person-years (median follow-up duration, 2.1 years). In the model adjusted for age and sex, the hazard ratio was 0.65 (95% confidence interval, 0.51 to 0.82), and statistical significance disappeared after adjustment for body mass index (BMI) and cardiometabolic factors. In the subgroup analyses, NAFLD was associated with a lower risk of incident BMD decrease in females even after adjustment for confounders. The direction of the effect of NAFLD on the risk of BMD decrease changed depending on BMI category and body fat percentage, although the impact was statistically insignificant. Conclusions: NAFLD had a significant protective effect on BMD in females. However, the effects may vary depending on BMI category or body fat percentage.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.2
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• pp.204-209
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• 2008

Non-alcoholic fatty liver disease (NAFLD) is typically associated with obesity and insulin resistance. Non-alcoholic steatohepatitis (NASH) is a more serious form of NAFLD. Although fibrosis is common in pediatric NASH, cirrhosis has been rarely reported. Patients with hypothalamic or pituitary dysfunction are at risk for obesity and insulin resistance with subsequent development of NAFLD. We report a case of NAFLD progressing to cirrhosis in an obese 16 year-old boy with hypopituitarism.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.133-139
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• 2018

Nonalcoholic steatohepatitis (NASH) is becoming common chronic liver disease because of the increasing global prevalence of obesity and consequently Nonalcoholic fatty liver disease (NAFLD). However, the mechanism for progression of NAFLD to NASH and then cirrhosis is not completely understood, yet. The triggering of these hepatic diseases is thought from hepatocyte injury caused by over-accumulated lipid toxicity. Injured hepatocytes release damage-associated molecular patterns (DAMPs), which can stimulate the Kupffer cells (KCs), liver-resident macrophages, to release pro-inflammatory cytokines and chemokines, and recruit monocyte-derived macrophages (MDMs). The increased activation of KCs and recruitment of MDMs accelerate the progression of NAFLD to NASH and cirrhosis. Therefore, characterization for activation of hepatic macrophages, both KCs and MDMs, is a baseline to figure out the progression of hepatic diseases. The purpose of this review is to discuss the current understanding of mechanisms of NAFLD and NASH, mainly focusing on characterization and function of hepatic macrophages and suggests the regulators of hepatic macrophages as the therapeutic target in hepatic diseases.