Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.
Humans ; Child ; Hepatitis B, Chronic/pathology* ; Retrospective Studies ; Case-Control Studies ; Hepatitis B virus/genetics* ; Liver Cirrhosis/pathology* ; Non-alcoholic Fatty Liver Disease/complications* ; Risk Factors

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

Objective: To explore the SNP effects of patatin-like phospholipase domain which containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2) gene, environmental effects of smoking, alcohol drinking and interaction between gene-gene, gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). Methods: We collected anticoagulant peripheral blood from patients of HBV-HCC, chronic hepatitis B (CHB), liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926, using the flight mass spectrometry method. The optimal assignment value of gene polymorphisms was defined by using the online SNP stats. Hardy-Weinberg (H-W) balance was tested for SNP. Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method. The gene-gene, gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods. Results: The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (χ(2)=11.980, P<0.005). Two loci frequency distributions in the other groups were all in accordandce with the H-W balance. After adjusting for influences on age and sex and comparing to the healthy group, the rs58542926 mutation appeared as OR=1.659, 95%CI: 1.026-2.684, P=0.039, in the HBV-HCC group. When comparing to CHB group, the HBV-HCC group presented that drinking as OR=1.680, 95%CI: 1.121-2.519, P=0.012. When comparing to the LC group, the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively, in the HBV-HCC group. When comparing to the CHB+LC group, interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885, P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965, P=0.024). As for drinking and mutation of rs738409, the multiplication model of logistic regression showed no statistically significant differences. Interaction between smoking and drinking appeared as OR=1.756 (P<0.001) in the logistics regression multiplication model. Conclusions: Factors as mutation of TM6SF2, smoking and drinking all appeared as risk factors for HBV-HCC. Mutations of both PNPLA3 and TM6SF2, together with smoking and drinking all served as risk factors for HBV-HCC. However, the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC.
Alcohol Drinking/adverse effects* ; Carcinoma, Hepatocellular/virology* ; Case-Control Studies ; Epistasis, Genetic ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Genotype ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Lipase/genetics* ; Liver Cirrhosis, Alcoholic/complications* ; Liver Neoplasms/virology* ; Membrane Proteins/genetics* ; Polymorphism, Single Nucleotide ; Smoking/adverse effects*

PURPOSE: The aldehyde dehydrogenase 2 (ALDH2) gene has been implicated in the development of alcoholic liver cirrhosis (ALC) in East Asians. However, the results are inconsistent. In this study, a meta-analysis was performed to assess the associations between the ALDH2 polymorphism and the risk of ALC. MATERIALS AND METHODS: Relevant studies were retrieved by searching PubMed, Web of Science, CNKI, Wanfang and Veipu databases up to January 10, 2015. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using either the fixed- or random effects model. RESULTS: A total of twelve case-control studies included 1003 cases and 2011 controls were included. Overall, the ALDH2 polymorphism was associated with a decreased risk of ALC (*1/*2 vs. *1/*1: OR=0.78, 95% CI: 0.61-0.99). However, in stratification analysis by country, we failed to detect any association among Chinese, Korean or Japanese populations. CONCLUSION: The pooled evidence suggests that ALDH2 polymorphism may be an important protective factor for ALC in East Asians.
Aldehyde Dehydrogenase, Mitochondrial/*genetics ; Asian Continental Ancestry Group/*genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Humans ; Liver Cirrhosis, Alcoholic/*ethnology/*genetics ; Odds Ratio ; Polymorphism, Genetic/*genetics ; Protective Factors

No abstract available.
Asian Continental Ancestry Group ; Flavobacteriaceae Infections ; Flavobacterium/*genetics/isolation & purification ; Humans ; Liver Cirrhosis, Alcoholic/blood/*diagnosis/microbiology ; Male ; Middle Aged ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; Republic of Korea ; Sequence Analysis, DNA

Many studies have suggested that occult HBV infection has a substantial clinical relevance to hepatocellular carcinoma (HCC). Occult HBV infection is an important risk factor for the development of cirrhosis and HCC in patients without HBsAg. As a matter of fact, occult HBV infection is one of the most common causes of crytogenic HCC in endemic areas of HBV. However, there still are controversial issues about the association between occult HBV infection and HCC according to the underlying liver disease. In alcoholic cirrhosis, occult HBV infection may exert synergistic effect on the development of HCC. However, there is insufficient evidence to relate occult HBV infection to hepatocarcinogenesis in non-alcoholic fatty liver disease. In cryptogenic HCC, occult HBV infection may play a direct role in the development of HCC. In order to elucidate the assocciation between occult HBV infection and HCC, underlying liver disease must be specified and larger number of cases must be included in future studies.
Carcinoma, Hepatocellular/*complications/*diagnosis/epidemiology ; DNA, Viral/analysis ; Hepatitis/complications ; Hepatitis B/*complications/*diagnosis/epidemiology ; Hepatitis B virus/genetics ; Humans ; Liver Cirrhosis, Alcoholic/complications ; Liver Neoplasms/*complications/*diagnosis/epidemiology ; Risk Factors

BACKGROUND/AIMS: Transforming growth factor beta1 (TGF-beta1) is a key cytokine in the production of extracellular matrix. A genetic polymorphism at codon 10 of the TGF-beta1 gene is associated with liver fibrosis. We investigated the effect of genetic polymorphisms at codon 10 on the development of alcoholic liver cirrhosis (ALC). METHODS: In total, 119 controls and 182 patients with ALC, were enrolled in the study. Clinical and laboratory data including total lifetime alcohol intake were collected at enrollment. The genotype at codon 10 was determined for each patient by single-strand conformation polymorphism. RESULTS: There were three types of genetic polymorphism at codon 10: homozygous proline (P/P), heterozygous proline/leucine (P/L), and homozygous leucine (L/L). Among the controls, the proportions of P/P, P/L, and L/L were 26.1%, 44.5%, and 29.4%, respectively in the ALC group, these proportions were 23.1%, 43.4%, and 33.5%, respectively. The genotype distribution did not differ between the controls and the ALC group. In the ALC group, age, total lifetime alcohol intake, and distribution of Child-Pugh class did not differ with the genotype. Of the male patients with ALC (n=164), the proportions of P/P, P/L, and L/L were 20.1%, 44.5%, and 35.4%, respectively the genotype distribution did not differ between the male controls and the male ALC patients. CONCLUSIONS: The genotype at codon 10 in TGF-beta1 does not appear to influence the development of ALC. Further study is needed to investigate other genetic factors that influence the development of ALC in patients with chronic alcohol intake.
Aged ; Alcohol Drinking ; Codon ; Female ; Genotype ; Heterozygote ; Homozygote ; Humans ; Liver Cirrhosis, Alcoholic/*genetics/pathology ; Male ; Middle Aged ; *Polymorphism, Genetic ; Transforming Growth Factor beta1/*genetics/metabolism

Animals ; Celecoxib ; Cyclooxygenase 1 ; genetics ; metabolism ; Cyclooxygenase 2 ; genetics ; metabolism ; Cyclooxygenase 2 Inhibitors ; pharmacology ; therapeutic use ; Cytokines ; metabolism ; Disease Models, Animal ; Ethanol ; adverse effects ; Fatty Liver, Alcoholic ; pathology ; prevention & control ; Immunohistochemistry ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Alcoholic ; pathology ; prevention & control ; Liver Diseases, Alcoholic ; pathology ; prevention & control ; Pyrazoles ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Sulfonamides ; pharmacology ; therapeutic use

BACKGROUND/AIMS: Alcohol and the hepatitis B virus (HBV) exert synergistic effects in hepatocelluar carcinogenesis. We aimed to elucidate the clinical significance of the antibody to hepatitis B core antigen (anti-HBc) and occult HBV infection on the development of hepatocellular carcinoma (HCC) in patients with alcoholic liver cirrhosis (LC). METHODS: Patients with alcoholic LC alone (n=193) or combined with HCC (n=36), who did not have HBsAg or antibody to hepatitis C virus were enrolled. Clinical data and laboratory data including anti-HBc were investigated at enrollment. The polymerase chain reaction was applied to HBV DNA using sera of patients with HCC or LC after age and sex matching. RESULTS: Patients with HCC were older (60+/-11 years vs. 53+/-10 years, mean+/-SD, P<0.001), more likely to be male (100% vs. 89%, P=0.03), and had a higher positive rate of anti-HBc (91.2% vs. 77.3%, P=0.067), and a higher alcohol intake (739+/-448 kg vs. 603+/-409 kg, P=0.076) than those with LC. Age was the only significant risk factor for HCC revealed by multiple logistic regression analysis (odds ratio, 1.056; P=0.003). The positive rate of anti-HBc and alcohol intake did not differ in age- and sex-matched subjects between the LC (n=32) and HCC (n=31) groups. However, the detection rate of serum HBV DNA was higher in the HCC group (48.4%) than in the LC group (0%, P<0.001). CONCLUSIONS: Anti-HBc positivity is not a risk factor for HCC. However, occult HBV infection may be a risk factor for HCC in patients with alcoholic LC.
Adult ; Aged ; Antibodies, Viral/blood ; Carcinoma, Hepatocellular/diagnosis/epidemiology/*etiology ; DNA, Viral/analysis ; Female ; Hepatitis B/*complications/diagnosis ; Hepatitis B Core Antigens/*immunology ; Hepatitis B Surface Antigens/immunology ; Hepatitis B virus/genetics/immunology/isolation & purification ; Hepatitis C/complications/diagnosis ; Humans ; Liver Cirrhosis, Alcoholic/*complications/diagnosis/epidemiology ; Liver Neoplasms/diagnosis/epidemiology/*etiology ; Male ; Middle Aged ; Risk Factors

BACKGROUND/AIMS: Susceptibility to organ damage induced by alcohol may be related to inherited variations (polymorphisms) in alcohol-metabolizing enzymes, or polymorphisms affecting cytokines. The aim of this study was to compare the genotype and allelic frequencies of ADH2, ADH3, ALDH2, cytochrome P450-2E1, IL-1, IL-6, IL-8 and tumor necrosis factor-alpha in patients with alcoholic pancreatitis and alcoholic liver cirrhosis with those of controls. METHODS: We determined the polymorphism of genes of the above-mentioned alcohol-metabolizing enzymes and cytokines in 29 alcoholic pancreatitis patients (AP), 22 alcoholic liver cirrhosis patients (LC) and 100 healthy blood donors (control). The genotypes were characterized by restriction fragment length polymorphism after amplification of genomic DNA by polymerase chain reaction. RESULTS: The allelic frequency of CYP2E1*c2 was significantly different in three groups (AP: LC: Control=0.224: 0.136: 0.320, p<0.05). There was no significant difference in the other genotypes or allelic frequencies of the three groups. The allelic frequencies of CYP2E1*c2 and ALDH2*2 were more frequent in the control than patients with alcoholic liver cirrhosis (LC: Control=0.136: 0.320, p<0.05, LC: Control= 0.114: 0.265, p<0.05). Allelic frequencies of ADH2 was statisitcally different between LC and control (ADH2*1; LC: Control=0.727: 0.495, ADH2*2; 0.227: 0.360, ADH2*3; 0.046: 0.145, p<0.05). CONCLUSIONS: There was no difference in the frequencies of genotype and allele of enzymes and cytokines among the three groups. However, frequency of ADH2*1 was significantly higher and those of CYP2E1*c2 and ALDH2*2 were significantly lower than LC group than control.
Adult ; Aged ; Alcohol Dehydrogenase/*genetics ; Aldehyde Dehydrogenase/*genetics ; Cytochrome P-450 CYP2E1/genetics ; Cytokines/*genetics ; English Abstract ; Female ; Gene Frequency ; Genotype ; Humans ; Liver Cirrhosis, Alcoholic/*genetics ; Male ; Middle Aged ; Pancreatitis, Alcoholic/*genetics ; *Polymorphism, Genetic