Prevalence and features of fatty liver detected by physical examination in Guangzhou

AIM:To investigate the prevalence of fatty liver discovered upon physical examination of Chinese patients and determine the associated clinical characteristics.METHODS:A total of 3433 consecutive patients who received physical examinations at the Huangpu Division of the First Affiliated Hospital at Sun Yat-sen University in Guangzhou,China from June 2010 to December2010 were retrospectively enrolled in the study.Results of biochemical tests,abdominal ultrasound,electrocardiography,and chest X-ray were collected.The diagnosis of fatty liver was made if a patient met any two of the three following ultrasonic criteria:(1)liver and kidney echo discrepancy and presence of an increased liver echogenicity(bright);(2)unclear intrahepatic duct structure;and(3)liver far field echo decay.RESULTS:The study population consisted of 2201males and 1232 females,with a mean age of 37.4±12.8 years.When all 3433 patients were considered,the overall prevalence of hyperlipidemia was 38.1%,of fatty liver was 26.0%,of increased alanine aminotransferase(ALT)and/or aspartate aminotransferase(AST)levels was 11.9%,of gallstone was 11.4%,of hyperglycemia was 7.3%,of hypertension was 7.1%,and of hyperuricemia was 6.2%.Of the 2605 patients who completed the abdominal ultrasonography exam,677(26.0%)were diagnosed with fatty liver and the prevalence was higher in males(32.5%vs females:15.3%,P<0.001).The overall prevalence of fatty liver increased with age,with the peak prevalence(39.5%)found in the 60 to 70-year-old age group.Among patients between the ages of 18 to 50-year-old,the prevalence of fatty liver was significantly higher in males(20.2%vs females:8.7%,P<0.001);the difference in prevalence between the two sexes in patients>50-year-old did not reach statistical significance.Only 430 of the patients diagnosed with fatty liver had complete information;among those,increased ALT and/or AST levels were detected in only 30%,with all disturbances being mild or moderate.In these 430 patients,the overall prevalence of hypertriglyceridemia was 31.4%,of mixed type hyperlipidemia was 20.9%,of hypercholesterolemia was 12.3%,of hyperglycemia was 17.6%,of hypertension was 16.0%,of hyperuricemia was 15.3%,and of gallstone was 14.4%.Again,the prevalences of hypertriglyceridemia and hyperuricemia were higher in males(hypertriglyceridemia,36.0%vs females:12.0%,P<0.05;hyperuricemia,17.3%vs females:7.2%,P<0.05);in contrast,however,the prevalences of mixed type hyperlipidemia and hypercholesterolemia was higher in females(mixed type hyperlipidemia,18.7% vs females:30.1%,P<0.05,hypercholesterolemia,9.5%vs females:24.1%,P<0.05).Finally,comparison of the fatty liver group to the non-fatty liver group showed that prevalences of hyperlipidemia,hyperglycemia,hypertension,and hyperuricemia were higher in the former(all P<0.01).CONCLUSION:A high prevalence of fatty liver is detected upon physical examination in Guangzhou,and the primary associated clinical findings are hyperlipidemia,hyperglycemia,hypertension,and hyperuricemia.

Interleukin-21 gene polymorphisms and chronic hepatitis B infection in a Chinese population

AIM: To investigate the relationship between inter-leukin-21(IL21) gene polymorphisms and chronic hepatitis B virus(HBV) infection in a Chinese population.METHODS: In this case-control study, 366 Chinese HBV-infected patients were recruited and divided into hepatocellular carcinoma(HCC; n = 94) and non-HCC(n = 272) groups at The First Affiliated Hospital of Sun Yat-Sen University, from April 2009 to December 2012.In the non-HCC group, the patients were classified into three clinical subsets, 76 patients had chronic hepatitis B, 101 were HBV carriers and 95 patients had HBV-related cirrhosis.Two hundred eight unrelated healthy controls were also included.Genomic DNA was extracted from peripheral blood.Single nucleotide polymorphisms(SNPs) rs13143866, rs2221903, and rs907715 were subsequently genotyped using the SNaP shot SNP technique.RESULTS: There were no significant differences in allele and genotype frequencies of SNPs rs13143866, rs2221903, and rs907715 between chronic HBVinfected patients and control subjects.Furthermore, no significant differences were found in the frequencies of all alleles and genotypes between the HCC group and the non-HCC group.However, in the subgroup analysis, IL21 rs13143866 genotype AA frequency in the HBV carrier group was higher than in controls(OR = 6.280, 95%CI: 1.238-31.854; P = 0.019), and the effect of the recessive model(AA vs GG + GA, OR = 6.505, 95%CI: 1.289-32.828) was observed in the HBV carrier group.IL21 rs2221903 genotype TC frequency in the HBV carrier group was higher than in controls(OR = 1.809, 95%CI: 1.043-3.139; P = 0.035).In the haplotype analysis, the ATA haplotype(rs13143866, rs2221903, and rs907715) of IL21 was more frequent in the HCC group than in the non-HCC group(0.165 vs 0.104, P = 0.044; OR = 1.700, 95%CI: 1.010-2.863).CONCLUSION: Genotypes rs13143866 AA and rs2221903 TC are risk factors for carrying HBV; ATA haplotype increases the risk of HBV-related HCC onsetin a Chinese population.

Apolipoprotein C3(-455T>C) polymorphism confers susceptibility to nonalcoholic fatty liver disease in the Southern Han Chinese population

AIM:To investigate the relationship between Apolipoprotein C3(APOC3)(-455T>C) polymorphism and nonalcoholic fatty liver disease(NAFLD) in the Southern Chinese han population.METHODS:In this prospective case-control study,we recruited 300 NAFLD patients and 300 healthy controls to a cohort representing Southern Chinese han population at The First Affiliated Hospital,Sun Yat-sen University,from January to December 2012. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing were used to genotype the APOC3(-455T>C) variants.RESULTS:After adjusting for age,gender,and bodymass index,TC and CC genotypes were found to increase the susceptibility to NAFLD compared to the TT genotype,with adjusted odds ratios(ORs) of 1.77(95%CI:1.16-2.72) and 2.80(95%CI:1.64-4.79),respectively. Further stratification analysis indicated that carriers of the CC genotype was more susceptible to insulin resistance(IR) than those of the TT genotype,with an OR of 3.24(95%CI:1.52-6.92). The CC genotype also was associated with a significantly higher risk of hypertension,hypertriglyceridemia,and low levels of high-density lipoprotein cholesterol(hDL)(P < 0.05). No association was found between the APOC3(-455T>C) polymorphism and obesity,impaired glucose tolerance,hyperuricemia,hypercholesterolemia,or high levels of low-density lipoprotein cholesterol(LDL)(P > 0.05).CONCLUSION:APOC3(-455T>C) genetic variation is involved in the susceptibility to developing NAFLD,IR,hypertension,hypertriglyceridemia,and low hDL in the Southern Chinese han population.

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease:A multicenter cross-sectional study in China

Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.

Association of keratin 8/18 variants with non-alcoholic fatty liver disease and insulin resistance in Chinese patients: A case-control study

AIM To test the hypothesis that K8/K18 variants predispose humans to non-alcoholic fatty liver disease(NAFLD) progression and its metabolic phenotypes. METHODS We selected a total of 373 unrelated adult subjects from our Physical Examination Department, including 200 unrelated NAFLD patients and 173 controls of both genders and different ages. Diagnoses of NAFLD were established according to ultrasonic signs of fatty liver. All subjects were tested for population characteristics, lipid profile, liver tests, as well as glucose tests. Genomic DNA was obtained from peripheral blood with a DNeasy Tissue Kit. K8/K18 coding regions were analyzed, including 15 exons and exon-intron boundaries. RESULTS Among 200 NAFLD patients, 10(5%) heterozygouscarriers of keratin variants were identified. There were 5 amino-acid-altering heterozygous variants and 6 non-coding heterozygous variants. One novel aminoacid-altering heterozygous variant(K18 N193S) and three novel non-coding variants were observed(K8 IVS5-9A→G, K8 IVS6+19G→A, K18 T195T). A total of 9 patients had a single variant and 1 patient had compound variants(K18 N193S+K8 IVS3-15C→G). Only one R341 H variant was found in the control group(1 of 173, 0.58%). The frequency of keratin variants in NAFLD patients was significantly higher than that in the control group(5% vs 0.58%, P = 0.015). Notably, the keratin variants were significantly associated with insulin resistance(IR) in NAFLD patients(8.86% in NAFLD patients with IR vs 2.5% in NAFLD patients without IR, P = 0.043).CONCLUSION K8/K18 variants are overrepresented in Chinese NAFLD patients and might accelerate liver fat storage through IR.

Metabolic Disorders Combined with Noninvasive Tests to Screen Advanced Fibrosis in Nonalcoholic Fatty Liver Disease

Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is associated with metabolic disorders.This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients.Methods:A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers.We compared the severity of fibrosis in patients with different components of metabolic disorders.Based on standard noninvasive tests and metabolic disorders,we developed new algorithms to identify advanced fibrosis.Results:Metabolic syndrome(MetS)was frequent in NAFLD patients(133/246,54%).Patients with MetS had a higher proportion of significant fibrosis(p=0.014)and higher LSM values(9.2 kPa,vs.7.4 kPa,p=0.002)than those without MetS.Patients with more metabolic disorders had higher fibrosis stages(p=0.017).Reduced highdensity lipoprotein cholesterol(odds ratio[OR]:2.241,95%confidence interval[CI]:1.004–5.002,p=0.049)and raised fasting glucose(OR:4.500,95%CI:2.083–9.725,p<0.001)were significantly associated with advanced fibrosis.Using these two metabolic disorders as a screening tool,a sensitivity,specificity and accuracy of 92%,81%and 83%was achieved,respectively.With the new algorithms combining metabolic disorders with noninvasive measurements,the number of patients requiring liver biopsy was reduced,especially in combination with the Fibrosis-4 score and metabolic disorders(36%to 17%,p<0.001).In addition,this stepwise algorithm could achieve a high accuracy(85%)and high negative predictive value(93%).Conclusions:Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis.With further validation and investigation,new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.