Recently, the prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing in Korean population. NAFLD includes a spectrum of hepatic pathology from simple steatosis in its most benign form, to nonalcoholic steatohepatitis (NASH) and/or cirrhosis. NAFLD has a strong association with type 2 diabetes and obesity, and thus it is now recognized to represent the hepatic manifestation of metabolic syndrome. The pathogenesis of simple steatosis occurrence and its progression to NASH is not entirely elucidated and multi-factorial. Liver fat accumulation is mainly induced by insulin resistance and increased free fatty acids, and then NASH is developed by oxidative stress, lipid peroxidation, mitochondrial dysfunction, gut-derived endotoxin, and cytokine/adipokine interplay. Genetic factors and environmental factors such as exercise and high fat and high fructose diet also participate in the development of NAFLD. This review is focused to summarize the up-to-date understanding of NAFLD pathogenesis.
Diet ; Fatty Acids, Nonesterified ; Fatty Liver ; Fibrosis ; Fructose ; Insulin Resistance ; Lipid Peroxidation ; Liver ; Obesity ; Oxidative Stress ; Prevalence

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease globally, and its prevalence is rapidly increasing. Nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD, is characterized by hepatocellular injury, inflammation, and fibrosis. Patients with NASH or severe fibrosis should be treated according to international NAFLD guidelines. Currently, regulatory agencies have not approved any pharmaceutical treatment for NAFLD. Vitamin E and pioglitazone are efficacious for NASH resolution; however, their benefits must be weighed against the reported risks. In a phase 2 trial, a glucagon-like peptide-1 agonist commonly used for diabetes and obesity was found to improve liver histology in patients with NASH. Furthermore, therapeutic agents targeting NASH pathogenesis, including bile acid signaling, insulin resistance, and lipid metabolism, are in various phases of clinical development. In this article, we review the benefits and drawbacks of current pharmacotherapy and the efficacy of upcoming treatments for NASH.

No abstract available.
Constriction, Pathologic* ; Humans ; Infant, Newborn* ; Pulmonary Artery* ; Systolic Murmurs*

BACKGROUND: The surfactant specific proteins, SP-B and SP-C are believed to be important regulators of the surfactant function and homeostasis. Since acute respiratory distress syndrome(ARDS) is usually viewed as the functional and morphological expression of a similar underlying lung injury caused by a variety of insults, and since abnormalities in the surfactant function have been described in ARDS, the authors investigated the different effects of endotoxin and thiourea on the accumulation of mRNA encoding SP-B and SP-C. METHODS: Sprague-Dawley rats were given 5 mg/kg of an intraperitoneal endotoxin from Salmonella enteritidis and 3.5 mg/kg intraperitoneal thiourea and were sacrificed at different time periods. RESULTS: 1. The SP-B mRNA levels 6 and 24 hours after the 5 mg/kg endotoxin treatment was significantly reduced by 26.1% and 50%, respectively(P<0.01, P<0.001). 2. The SP-B mRNA levels 24 hours after the 3.5 mg/kg thiourea treatment was reduced by 9.8% and 12.5%, respectively. 3. The SP-C mRNA levels 6 and 24 hours after the 5 mg/kg endotoxin treatment was significantly reduced by 38.7% and 53.6%, respectively(P<0.01, P<0.001). 4. The SP-C mRNA level 6 hours after the 3.5 mg/kg thiourea treatment was reduced by 22.8%(P<0.05). CONCLUSION: These results indicate that the differential regulation of the hydrophobic surfactant proteins in vivo is evident, and suggest that the hydrophobic surfactant proteins might be differentially regulated during lung injury at different time periods without altering the lung wet to dry ratios. The mechanism of these alternations at the different time periods and the different kinds of etiology remain to be determined.
Animals ; Gene Expression* ; Homeostasis ; Lung ; Lung Injury ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger ; Salmonella enteritidis ; Thiourea*

H2-receptor blockers are widely used for therapy of peptic ulcer disease and gastroesophageal reflux disease. H2-receptor blockers infrequently cause adverse hepatic effects, and when they occur they are usually asymptomatic. There are several previous reports of liver injury related to ranitidine. Until now, only two cases of acute hepatitis associated with the use of famotidine were reported in the world. We report three cases of clinical hepatitis that followed administration of famotidine (2 cases) and ranitidine (1 case). First, a 54-year-old woman received famotidine, 40mg, daily for treatment of erosive gastritis. After 6 weeks of treatment with famotidine, jaundice and itching sense developed. Second, a 45-year-old man was hospitalized for jaundice. He had a long history of duodenal ulcer and had been intermittently treated with famotidine. He had 6 weeks of treatment with famotidine prior to admission. Third, a 19-year-old woman was hospitalized for nausea, vomiting and urticaria. She had a history of acute hepatitis B virus infection and was discharged 4 weeks prior to readmission. She had been received ranitidine, 300 mg, daily for treatment of gastritis. After 17 days of drug ingestion, whenever she had taken her medication, she developed these symptoms of nausea, vomiting and urticaria. Other causes of hepatitis were ruled out and all patients recovered after discontinuation of drug ingestion.
Duodenal Ulcer ; Eating ; Famotidine* ; Female ; Gastritis ; Gastroesophageal Reflux ; Hepatitis B virus ; Hepatitis* ; Humans ; Jaundice ; Liver ; Middle Aged ; Nausea ; Peptic Ulcer ; Pruritus ; Ranitidine* ; Urticaria ; Vomiting ; Young Adult

H2-receptor blockers are widely used for therapy of peptic ulcer disease and gastroesophageal reflux disease. H2-receptor blockers infrequently cause adverse hepatic effects, and when they occur they are usually asymptomatic. There are several previous reports of liver injury related to ranitidine. Until now, only two cases of acute hepatitis associated with the use of famotidine were reported in the world. We report three cases of clinical hepatitis that followed administration of famotidine (2 cases) and ranitidine (1 case). First, a 54-year-old woman received famotidine, 40mg, daily for treatment of erosive gastritis. After 6 weeks of treatment with famotidine, jaundice and itching sense developed. Second, a 45-year-old man was hospitalized for jaundice. He had a long history of duodenal ulcer and had been intermittently treated with famotidine. He had 6 weeks of treatment with famotidine prior to admission. Third, a 19-year-old woman was hospitalized for nausea, vomiting and urticaria. She had a history of acute hepatitis B virus infection and was discharged 4 weeks prior to readmission. She had been received ranitidine, 300 mg, daily for treatment of gastritis. After 17 days of drug ingestion, whenever she had taken her medication, she developed these symptoms of nausea, vomiting and urticaria. Other causes of hepatitis were ruled out and all patients recovered after discontinuation of drug ingestion.
Duodenal Ulcer ; Eating ; Famotidine* ; Female ; Gastritis ; Gastroesophageal Reflux ; Hepatitis B virus ; Hepatitis* ; Humans ; Jaundice ; Liver ; Middle Aged ; Nausea ; Peptic Ulcer ; Pruritus ; Ranitidine* ; Urticaria ; Vomiting ; Young Adult

Kawasaki disease is an acute febrile vasculitis affecting primarily infants and young children. In addition to the cardiovascular involvement, it may cause inflammatory changes in various organs and body systems : digestive, respiratory, urinary, nervous and musculoskeletal. A case is reported of atypical Kawasaki disease associated with acute renal failure and necrotizing myositis in the right gastrocnemius in a 10-year-old boy. In older children, uncommon age of onset and additional features less commonly associated with Kawasaki disease may contribute to a delayed diagnosis.
Acute Kidney Injury* ; Age of Onset ; Child ; Delayed Diagnosis ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome* ; Myositis* ; Vasculitis

BACKGROUND/AIMS: Liver biopsy has been used to evaluate the degree of hepatic fibrosis in patients with chronic liver diseases. It is important to assess liver fibrosis when following the course of chronic liver diseases. Histopathological examination of percutaneous biopsy specimens is invasive and is also of questionable value because of the heterogenous distribution of pathological changes in the liver. Therefore, non-nvasive methods to determine the progress of liver fibrosis are needed. Serum hyaluronic acid and type IV collagen are known to be related to hepatic fibrosis. This study was performed to evaluate the clinical usefulness of serum hyaluronic acid and type IV collagen measurement as a differential point in patients with chronic liver diseases and early cirrhosis. METHODS: This study included 109 patients with chronic liver diseases caused by various etiologies. Liver biopsy and histopathological classification were done in all patients. Serum hyaluronic acid and type IV collagen were measured by one-tep sandwich binding protein assay and one-tep sandwich enzyme immunoassay. RESULTS: The concentrations of hyaluronic acid and type IV collagen in the early cirrhosis group (208.5+/-186.4 ng/mL, 242.1+/-162.8 ng/mL) were significantly higher (p<0.01) than those in the normal and fatty liver group (26.3+/-21.7 ng/mL, 79.2+/-28.8 ng/mL), mild chronic hepatitis group (22.8+/-15.4 ng/mL, 125.5+/-79.7 ng/mL), moderate to severe hepatitis group (66.3+/-60.5 ng/mL, 148.5+/-78.7 ng/mL). At the cutoff value of 100 ng/mL for hyaluronic acid and 200 ng/mL for type IV collagen, the sensitivities were 66.7% and 55.6%, and specifities were 82.9% and 89%, and diagnostic efficiencies were 78.9% and 80.7% respectively for discriminating patients with cirrhosis (4 points) from the mild to severe fibrosis (0~3 points). CONCLUSIONS: The serum levels of hyaluronic acid and type IV collagen may be sensitive markers of fibrotic process in chronic liver diseases and useful biochemical markers in differentiation of the patients with early cirrhosis from those with chronic liver diseases.
Biomarkers ; Biopsy ; Carrier Proteins ; Classification ; Collagen Type IV* ; Fatty Liver ; Fibrosis ; Hepatitis ; Hepatitis, Chronic* ; Humans ; Hyaluronic Acid* ; Immunoenzyme Techniques ; Liver Cirrhosis* ; Liver Diseases ; Liver*

Clinical management of chronic hepatitis B is rapidly evolving after the recent development of new antiviral drugs. These agents have been shown to be effective in improving virological, biochemical, and histological features in high proportion of the patients with chronic hepatitis B. However, these drugs can not eliminate hepatitis B virus (HBV) directly. It can only suppress HBV replication. Furthermore, the emergence of drug resistant HBV has become problematic according to the long-term use of oral antiviral drugs. Therefore, physicians should be careful in selecting whom to treat, when to start treatment, how long to treat, how to monitor patients before, during and after the treatment, which drug to choose, and how to manage patients with drug resistance. This review will focus on the monitoring and treatment strategy for chronic hepatitis B and drug resistant hepatitis B, quoting some clinical data of recently introduced or promising future drugs.
Alanine Transaminase/blood ; Antiviral Agents/*therapeutic use ; *Drug Resistance, Viral ; Hepatitis B e Antigens/blood ; Hepatitis B virus/*drug effects ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Reverse Transcriptase Inhibitors/therapeutic use

OBJECTIVE: The presence of the various cytokines in human peritoneal fluid has been evaluated incompletely. Changes in cytokine lefels may be related to activation of peritoneal macrophage and T-lymphocyte, development of endometriosis, and infertility. This study assesses peritoneal fluid levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) in infertile women with endometriosis and normal women without endometriosis. Design : Prospective and case-control study in university hospital. MATERIALS AND METHODS: Cytokine levels in peritoneal fluid obtained during laparotomy or laparoscopy from 21 patients in infertile patients in infertile patients with endometriosis and 24 controls undergoing laparotomy or laparoscopy with no evidence of pelvic endometriosis were determined by enzymelinked immunosorbent assay. RESULTS: The mean levels of interleukin-6 in infertile patients with endometriosis and controls were 72.7+/-23.7 pg/ml and 18.5+/-9.7 pg/ml respectively (p=0.02). Similarly, the mean levels of interleukin-8 in infertile patients with endometriosis was significantly higher than that of controls (445.0+/-89.6, vs 45.1+/-48.4, p=0.04). The mean concentration of interleukin-10 in infertile patients with endometriosis was significantly lower than that of controls (1.09+/-0.04 vs 2.19+/-0.03, p=0.03). The level of tumor necrosis factor-alpha was not significantly different between the two study groups. CONCLUSIONS: Increased IL-6 and IL-8 and decreased IL-10 levels in the peritoneal fluid may be related to pathogenesis in the endometriosis and infertility, suggesting that partially contribute to the disturbed immune regulation observed in infertili women with endometriosis.
Ascitic Fluid* ; Case-Control Studies ; Cytokines ; Endometriosis* ; Female ; Humans ; Infertility ; Interleukin-10 ; Interleukin-6 ; Interleukin-8 ; Laparoscopy ; Laparotomy ; Macrophages, Peritoneal ; Prospective Studies ; T-Lymphocytes ; Tumor Necrosis Factor-alpha