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Objective:To investigate the pathological characteristics in chronic HBV infection patients with different upper limits of alanine aminotransferase (ALT) normal values and the influencing factors of liver tissue injury.Methods:The clinical data of 667 chronic HBV infection patients with ALT<40 U/L and HBV DNA loads >30 IU/mL who received liver biopsy in Zhenhai District Hospital of Traditional Chinese Medicine and Hwa Mei Hospital from January 2014 to December 2020 were retrospectively analyzed. The enrolled patients were divided into ALTⅠ group (<30 U/L for males, <19 U/L for females), ALTⅡ group (≥30 U/L and <35 U/L for males, ≥19 U/L and <25 U/L for females) and ALT Ⅲ group (≥35 U/L and <40 U/L for males, ≥25 U/L and <40 U/L for females). According to the degree of liver inflammation (G) and fibrosis stage (S), the enrolled patients were divided into non-significant damage group (G<2 and S<2) and significant damage group (≥G2 or/and ≥S2). Ridit analysis was used to compare the G/S composition ratio among three ALT groups, Logistic regression was used to analyze the risk factors of liver injury, the receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to analyze the optimal diagnostic threshold of ALT.Results:There were significant differences in the composition ratio of G and S among the three ALT groups( χ2=13.926 and 14.702, both P<0.001). The constituent ratios of significant liver pathological damage in the three groups of ALT levels were 26.05% (99/380), 32.03% (41/128) and 46.54% (74/159), respectively( χ2=21.596, P<0.001). Multivariate logistic regression analysis showed that high white/globulin ratio and PLT counts( OR=0.246 and 0.986, both P<0.001)were the protective factors for liver tissue injury; while negative HBcAg staining and elevated ALT and GGT levels ( OR=3.797, 1.053 and 1.013, P<0.001 or <0.05) were the risk factors of liver injury. ROC curve demonstrated the ALT threshold of liver tissue damage in male and female patients were 25.6 U/L and 25.5 U/L. Conclusions:In chronic HBV infection patients with normal ALT, with the increase of ALT level, the degree of liver tissue pathological damage may become more severe. The study demonstrates that it is necessary to lower the ALT threshold for protecting patients from liver tissue pathological damage.
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Objective:To establish and evaluate a new diagnostic model for significant liver tissue damage in patients with chronic hepatitis B virus (HBV) infection in the immune tolerance phase.Methods:The clinical data of 275 chronic HBV infection patients in the immune tolerance phase who underwent liver biopsy from January 2015 to November 2020 in the Hwa Mei Hospital, University of Chinese Academy of Sciences were included. According to the liver pathological changes, patients were divided into <G2 group and ≥G2 group, <S2 group and ≥S2 group, non-significant liver pathological damage group (GS0 group, <G2+ <S2) and significant liver pathological damage group (GS1 group, G2 and/or ≥S2). The liver pathological changes and clinical features were analyzed to establish the diagnostic model. The prediction value of the model was compared. Statistical analysis was conducted by linear regression analysis, and the area under the receiver operating characteristic curve, sensitivity and specificity for the diagnostic value of the model were calculated.Results:Among 275 patients, 43 cases (15.64%) had liver histologic activity ≥G2, 30 cases (10.91%) with liver fibrosis ≥S2, and 55 cases (20.00%) with liver damage of GS1. The correlated independent risk factors associated with significant liver pathological damage were age, levels of hepatitis B e antigen, γ-glutamyl transpeptidase, platelet count, alkaline phosphatase and alanine aminotransferase (all P<0.050). The diagnostic model of Y G/S was established according to these factors. The diagnostic efficacy of Y G/Swas highest for patients with liver histologic activity≥G2 and liver pathological damage GS1, with the areas under the curve of 0.783 and 0.811, respectively. The threshold of Y G/S was 0.18, with the sensitivity, specificity and negative predictive value of 0.782, 0.736 and 93.10%, respectively. When Y G/S <0.05, the sensitivity, negative predictive value and negative likelihood ratio were 0.982, 97.96% and 0.08, respectively. When Y G/S≥0.25, the specificity and positive likelihood ratio were 0.905 and 5.14, respectively. When Y G/S≥0.30, the specificity and positive likelihood ratio were 0.959 and 9.33, respectively. Conclusions:Approximately 20.00% of patients with chronic HBV infection in immune tolerance phase have significant liver pathological damage. The diagnostic model of Y G/S (<0.05 or ≥0.30) has certain evaluation value for significant liver pathological damage, and could help these patients avoid liver biopsy to a certain extent.
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Objective:To analyze the liver pathology, clinical characteristics and influence factors in patients with chronic hepatitis B virus (HBV) infection in immune tolerant phase (IT).Methods:The clinical data of 273 patients in IT phase who underwent liver biopsy from January 2015 to December 2019 were included in this study. The correlation between liver pathological changes and clinical features was analyzed.Results:There were 43 cases (15.75%) with liver histologic activity ≥ G2, 30 cases (10.99%) with liver fibrosis ≥ S2, and 55 cases (20.15%) with liver pathology ≥ G2 and/or ≥ S2. A total of 17.95% patients had liver steatosis. The majority (98.17%) of tissue samples were positive for HBsAg staining, while only 79.49% were positive for HBcAg. The characteristics of liver pathology were comparable in men from women patients. The differences of G and S were not statistically significant according to different HBsAg positivity, while those were statistically significant according to different HBcAg positivity. By univariate and multivariate analysis, the independent risk factors of pathological severity were HBcAg intensity, HBeAg level, and age. However, the differences of liver histologic activity and fibrosis were not statistically significant between those younger than 30 years old group from those older than 30 years old, neither between those younger or older than 40. Although the diagnostic value of liver inflammation and fibrosis 5 (LIF-5) was better than that of aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis 4 score (FIB-4), three diagnostic models for predicting the pathological severity were not strong enough (all area under the curves<0.8). Only the specificity of LIF-5 for predicting≥ G2, ≥ G2 and/or ≥ S2 was over 80%.Conclusions:Approximately 20% patients with chronic HBV infection in IT phase have progressive liver inflammation or fibrosis. The intensity of liver HBcAg and HBeAg level are negatively correlated with the severity of disease. The diagnostic models or most clinical indicators have low predictive effect for chronic HBV infections in IT phase.
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<p><b>OBJECTIVE</b>To identify secondary mutations associated with deafness in a Chinese family affected with deafness.</p><p><b>METHODS</b>The family has been subjected to clinical and molecular analyses, in addition with measurement of reactive oxygen species and doubling time after establishment of immortalized lymphocyte cell lines.</p><p><b>RESULTS</b>The results showed that the hearing loss level and audiometric configuration were discrepant among the family members with maternally transmitted hearing loss. The penetrance of hearing loss in this family was respectively 66.7% and 44.4% when aminoglycoside-induced hearing loss was included or excluded. Analysis of whole mitochondrial genome has found 33 variants as previously reported polymorphisms, except for a 12s rRNA A1555G mutation and a tRNA(Thr)T15943C mutation. Haplotype evolutionary tree has verified that this family belonged to East-Asian haplogroup F. 15943 position was located on the T-stem of the tRNA(Thr), which has destroyed the extremely conserved T-A base pair when T changed to C at this position. However, functional experiments indicated that the population doubling time in special galactose and glucose were longer, whilst the level of reactive oxygen species has increased. Compared with the control cell line groups and a family only carrying the 12s rRNA A1555G mutation, all of the three groups belonged to the same haplogroup.</p><p><b>CONCLUSION</b>Mitochondrial tRNA(Thr)T15943C mutation may act as a potential modifying factor and interact with 12s rRNA A1555G mutation, and thereby enhance the penetrance and expression of deafness.</p>
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Asian People , Genetics , Base Sequence , China , DNA, Mitochondrial , Genetics , Deafness , Genetics , Molecular Sequence Data , Pedigree , Phenotype , Point Mutation , RNA, Ribosomal , Genetics , RNA, Transfer, Thr , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the correlation between nonsyndromic deafness and mitochondrial 12s rRNA A839G mutation.</p><p><b>METHODS</b>According to the clinical manifestations of mitochondrial DNA sequencing and analysis to find and determine family containing mitochondrial 12s rRNA A839G mutation. Harvested its family members blood and transferred their lymphocytes into lymphoblastoid cell lines, followed by cells cultured, cell doubling experiment, susceptibility testing, cellular oxygen consumption rate experiment, ROS and mitochondrial membrane potential experimental tests were progressed to explore the correlation between the A839G mutation and nonsyndromic deafness.</p><p><b>RESULTS</b>The mitochondrial 12s rRNA A839G mutation pedigrees were determined through the full sequence detections of the Mitochondrial DNA, further phylogenetic analysis showed that 839 point conservative index (CI) up to 78.6%; in RPMI-galactose medium containing A839G gene mutant cell line, the doubling time was significantly longer than the control group, and the difference was significant (P = 0.033). The effect to cell lines containing the A839G mutation of aminoglycoside drugs was not obvious. When compared with the control group, cell lines containing the A839G mutation significantly reduced cellular oxygen consumption rate(P = 0.033); compared with the control group, the ROS levels of cell lines containing the A839G mutation appeared more substantial elevated with significan difference (P < 0.01). The mitochondrial membrane potential of cells of experimental group was significantly reduced than the control group.</p><p><b>CONCLUSION</b>The present study proved that the mitochondria 12s rRNA A839G mutations affect the function of the mitochondrial respiratory chain at the cell level, which might reduce the growth rate of the mutant cell lines, result in hearing.</p>