Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The global prevalence of pediatric NAFLD from general populations is 7.6%. In obese children, the prevalence is higher in Asia. NAFLD has a strong heritable component based on ethnic difference in the prevalence and clustering within families. Genetic polymorphisms of patatin-like phospholipase domain–containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2, and glucokinase regulatory protein (GCKR) are associated with the risk of NAFLD in children. Variants of PNPLA3 and GCKR are more common in Asians. Alterations of the gut microbiome might contribute to the pathogenesis of NAFLD. High fructose intake increases the risk of NAFLD. Liver fibrosis is a poor prognostic factor for disease progression to cirrhosis. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction are more accurate for steatosis quantification than ultrasound. Noninvasive imaging methods to assess liver fibrosis, such as transient elastography, shear-wave elastography, and magnetic resonance elastography are useful in predicting advanced fibrosis, but they need further validation. Longitudinal follow-up studies into adulthood are needed to better understand the natural history of pediatric NAFLD.
Asia ; Asian Continental Ancestry Group ; Child ; Diagnosis ; Disease Progression ; Elasticity Imaging Techniques ; Epidemiology ; Fibrosis ; Follow-Up Studies ; Fructose ; Gastrointestinal Microbiome ; Genetics ; Glucokinase ; Humans ; Liver Cirrhosis ; Liver Diseases ; Magnetic Resonance Spectroscopy ; Microbiota ; Natural History ; Non-alcoholic Fatty Liver Disease ; Phospholipases ; Polymorphism, Genetic ; Prevalence ; Protons ; Ultrasonography

BACKGROUND: Transient elastography (FibroScan®) is a non-invasive and rapid method for assessing liver fibrosis. While the feasibility and usefulness of FibroScan® have been proven in adults, few studies have focused on pediatric populations. We aimed to determine the feasibility and usefulness of FibroScan® in Korean children. METHODS: FibroScan® examinations were performed in 106 children (age, 5–15 years) who visited the Konyang University Hospital between June and September 2018. Liver steatosis was measured in terms of the controlled attenuation parameter (CAP), while hepatic fibrosis was evaluated in terms of the liver stiffness measurement (LSM). Children were stratified into obese and non-obese controls, according to body mass index (≥ or < 95th percentile, respectively). RESULTS: The obese group was characterized by significantly higher levels of aspartate aminotransferase (AST, 57.00 ± 48.47 vs. 26.40 ± 11.80 IU/L; P < 0.001) and alanine aminotransferase (ALT, 91.27 ± 97.67 vs. 16.28 ± 9.78 IU/L; P < 0.001), frequency of hypertension and abdominal obesity (abdominal circumference > 95% percentile) (P < 0.001), CAP (244.4–340.98 dB/m), and LSM (3.85–7.77 kPa) (P < 0.001). On FibroScan®, 30 of 59 obese children had fibrosis (LSM > 5.5 kPa), whereas the remaining 29 did not (LSM < 5.5 kPa). Obese children with fibrosis had higher levels of AST (73.57 ± 56.00 vs. 39.86 ± 31.93 IU/L; P = 0.009), ALT (132.47 ± 113.88 vs. 48.66 ± 51.29 IU/L; P = 0.001), and gamma-glutamyl transferase (106.67 ± 69.31 vs. 28.80 ± 24.26 IU/L; P = 0.042) compared to obese children without fibrosis. LSM had high and significant correlation (P < 0.05) with AST, ALT, homeostasis model assessment for insulin resistance, and AST-to-platelet ratio index. CONCLUSION: FibroScan® is clinically feasible and facilitates non-invasive, rapid, reproducible, and reliable detection of hepatic steatosis and liver fibrosis in the Korean pediatric population.
Adult ; Alanine Transaminase ; Aspartate Aminotransferases ; Body Mass Index ; Child ; Diagnosis ; Elasticity Imaging Techniques ; Fatty Liver ; Fibrosis ; Homeostasis ; Humans ; Hypertension ; Insulin Resistance ; Liver Cirrhosis ; Liver ; Methods ; Non-alcoholic Fatty Liver Disease ; Obesity, Abdominal ; Transferases

BACKGROUND AND PURPOSE: To test whether alcohol intake, both observational and estimated by genetic instruments, is associated with risk of ischemic and haemorrhagic stroke. METHODS: We used data from the Copenhagen City Heart Study 1991 to 1994 and 2001 to 2003, and the Copenhagen General Population Study 2003 to 2012 (n=78,546). As measure of alcohol exposure, self-reported consumption and genetic variation in alcohol metabolizing genes (alcohol dehydrogenase ADH1B and ADH1C) as instrumental variables were used. Stroke diagnoses were obtained from a validated hospital register. RESULTS: During follow-up 2,535 cases of ischemic and haemorrhagic stroke occurred. Low and moderate alcohol intake (1 to 20 drinks/week) was associated with reduced risk of stroke. The hazard ratios associated with drinking 1 to 6, 7 to 13, and 14 to 20 drinks/week were 0.84 (95% confidence interval [CI], 0.76 to 0.92), 0.83 (95% CI, 0.73 to 0.94), and 0.84 (95% CI, 0.73 to 0.97), respectively, compared with drinking < 1 drink/day. ADH1B and ADH1C genotypes were not associated with risk of stroke. Further analysis to test the included measures revealed that increasing alcohol intake (per 1 drink/day) was positively associated with risk of alcoholic liver cirrhosis, but not associated with risk of stroke, and that increasing blood pressure (per systolic 10 mm Hg) was not associated with risk of alcoholic liver cirrhosis, but positively associated with risk of stroke. CONCLUSIONS: Low and moderate self-reported alcohol intake was associated with reduced risk of stroke. The result was not supported by the result from the causal genetic analysis.
Alcohol Drinking ; Blood Pressure ; Diagnosis ; Drinking ; Follow-Up Studies ; Genetic Variation ; Genotype ; Heart ; Incidence ; Liver Cirrhosis, Alcoholic ; Oxidoreductases ; Prospective Studies ; Stroke*

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is prevalent in both economically developed and developing countries. Twenty percent of NASH progresses to cirrhosis with/without hepatocellular carcinoma, and there is an urgent need to find biomarkers for early diagnosis and monitoring progression of the disease. Using immunohistochemical and immunoelectron microscopic examination we previously reported that expression of matrix metalloproteinase-1 (MMP-1) increased in monocytes, Kupffer cells and hepatic stellate cells in early stage NASH. The present study investigated whether serum MMP-1 levels reflect disease activity and pharmaceutical effects in NASH patients. METHODS: We measured the serum levels of MMPs, tissue inhibitors of metalloproteinases (TIMPs), and several cytokines/chemokines in patients with histologically proven early and advanced stages of NASH and compared them with those in healthy controls. RESULTS: Serum MMP-1 levels in stage 1 fibrosis, but not in the more advanced fibrosis stages, were significantly higher than in healthy controls (P=0.019). There was no correlation between serum MMP-1 level and fibrosis stage. Serum MMP- 1 levels in NASH patients represented disease activity estimated by serum aminotransferase values during the follow-up period. In contrast, MMP-2, MMP-9 and TIMPs did not change with disease activity. Consistent with the finding that MMP-1 is expressed predominantly in monocytes and Kupffer cells, serum levels of monocyte chemotactic protein-1 and granulocyte-colony stimulating factor were significantly increased in NASH with stage 1 fibrosis. CONCLUSIONS: These results suggest that serum MMP-1 levels represent disease activity and may serve as a potential biomarker for monitoring the progression of NASH.
Biomarkers ; Carcinoma, Hepatocellular ; Chemokine CCL2 ; Cytokines ; Developing Countries ; Early Diagnosis ; Fibrosis* ; Follow-Up Studies ; Hepatic Stellate Cells ; Humans ; Kupffer Cells ; Liver Cirrhosis ; Matrix Metalloproteinase 1* ; Matrix Metalloproteinases ; Metalloproteases ; Monocytes ; Non-alcoholic Fatty Liver Disease*

Non-alcoholic fatty liver disease has been observed in over 30% of patients who have received tamoxifen therapy. However, tamoxifen-induced non-alcoholic steatohepatitis (NASH) cirrhosis has never been reported in Korea. A 41-year-old woman was diagnosed with invasive ductal carcinoma in the left breast. She had well-controlled type 2 diabetes mellitus, hypertension, and chronic hepatitis B. Ultrasonography showed mild fatty liver. Chronic hepatitis B had been treated with clevudine one month before the diagnosis of breast cancer. The patient was diagnosed with NASH cirrhosis 39 months after tamoxifen treatment. Careful observation for the development of NASH cirrhosis is warranted during tamoxifen therapy.
Adult ; Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Diabetes Mellitus, Type 2 ; Diagnosis ; Fatty Liver* ; Female ; Fibrosis* ; Hepatitis B, Chronic ; Humans ; Hypertension ; Korea ; Liver Cirrhosis ; Non-alcoholic Fatty Liver Disease ; Tamoxifen ; Ultrasonography

Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Decision Making ; End Stage Liver Disease ; complications ; diagnosis ; therapy ; Hepatitis B ; complications ; Humans ; Liver ; pathology ; Liver Cirrhosis ; complications ; diagnosis ; therapy ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; therapy ; Prognosis ; Referral and Consultation ; Treatment Outcome

Bile canalicular antibody (BCA) was first reported in 1969. Many studies of BCA were performed in the 1970s and 1980s and revealed that BCA has a highly positive rate in chronic active hepatitis and primary biliary cirrhosis (PBC). These studies suggested that BCA can be useful in the diagnosis of these liver diseases. However, BCA is almost negative in patients with alcoholic hepatitis. We report a case of BCA in a 50-yr-old woman with a history of heavy alcohol consumption. The patient's serum levels of aspartate transaminase and alanine transaminase were increased, leading to a diagnosis of alcoholic hepatitis. The patient was evaluated for liver disease. Anti-mitochondria antibody, anti-smooth muscle antibody, and anti-liver kidney microsomal antibody tests were conducted, yielding negative results. However, during this testing process, the patient's serum was incidentally found to be positive for BCA at a titer of 1:160. This is the first case report of BCA in Korea.
Alanine Transaminase ; Alcohol Drinking ; Alcoholics* ; Aspartate Aminotransferases ; Bile* ; Diagnosis ; Female ; Hepatitis, Alcoholic* ; Hepatitis, Chronic ; Humans ; Kidney ; Korea ; Liver Cirrhosis, Biliary ; Liver Diseases

Alcoholic liver disease (ALD) is a leading cause of cirrhosis, liver cancer, and acute and chronic liver failure and as such causes significant morbidity and mortality. While alcohol consumption is slightly decreasing in several European countries, it is rising in others and remains high in many countries around the world. The pathophysiology of ALD is still incompletely understood but relates largely to the direct toxic effects of alcohol and its main intermediate, acetaldehyde. Recently, novel putative mechanisms have been identified in systematic scans covering the entire human genome and raise new hypotheses on previously unknown pathways. The latter also identify host genetic risk factors for significant liver injury, which may help design prognostic risk scores. The diagnosis of ALD is relatively easy with a panel of well-evaluated tests and only rarely requires a liver biopsy. Treatment of ALD is difficult and grounded in abstinence as the pivotal therapeutic goal; once cirrhosis is established, treatment largely resembles that of other etiologies of advanced liver damage. Liver transplantation is a sound option for carefully selected patients with cirrhosis and alcoholic hepatitis because relapse rates are low and prognosis is comparable to other etiologies. Still, many countries are restrictive in allocating donor livers for ALD patients. Overall, few therapeutic options exist for severe ALD. However, there is good evidence of benefit for only corticosteroids in severe alcoholic hepatitis, while most other efforts are of limited efficacy. Considering the immense burden of ALD worldwide, efforts of medical professionals and industry partners to develop targeted therapies in ALF has been disappointingly low.
Acetaldehyde ; Adrenal Cortex Hormones ; Alcohol Drinking ; Alcoholics* ; Biopsy ; Carcinoma, Hepatocellular ; Diagnosis ; End Stage Liver Disease ; Fibrosis ; Genome, Human ; Hepatitis, Alcoholic ; Humans ; Liver ; Liver Cirrhosis ; Liver Diseases, Alcoholic* ; Liver Transplantation ; Malnutrition ; Mortality ; Prognosis ; Recurrence ; Risk Factors ; Tissue Donors

Although Dieulafoy lesion can occur in any part of the gastrointestinal tract, its occurrence in the rectum is rare. Rectal Dieulafoy lesions have been associated with advanced age, renal failure, burns, liver transplantation and cirrhosis. Here, we report on a case of massive bleeding from a rectal Dieulafoy lesion after lung decortication surgery in a 57-year-old male patient with alcoholic cirrhosis. Although rare, a rectal Dieulafoy lesion should be included in the differential diagnosis of massive lower gastrointestinal bleeding in a patient with cirrhosis.
Alcoholics* ; Burns ; Diagnosis, Differential ; Fibrosis ; Gastrointestinal Tract ; Hemorrhage* ; Humans ; Liver Cirrhosis ; Liver Cirrhosis, Alcoholic* ; Liver Transplantation ; Lung ; Male ; Middle Aged ; Rectum ; Renal Insufficiency

Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic liver disorders, and its incidence is expected to increase rapidly in the future as the rate of obesity increases and populations age. The gold standard for diagnosing NAFLD is liver biopsy, which involves sample error, high cost, and can be complicated due to its invasive nature. Therefore, many studies have been reported to establish accurate and convenient models to detect NAFLD using clinical and laboratory parameters. Most were derived from relatively small number of subjects and lack external validation, especially in the Korean population. This article summarizes the established and emerging risk factors for NAFLD and reviews non-invasive diagnostic algorithms for NAFLD including hepatic fibrosis.
Biopsy ; Diagnosis* ; Fibrosis ; Incidence ; Liver ; Liver Cirrhosis ; Non-alcoholic Fatty Liver Disease* ; Obesity ; Risk Factors