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OBJECTIVES@#Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT).@*METHODS@#This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored.@*RESULTS@#Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910).@*CONCLUSIONS@#The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
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Humanos , Hepatite B Crônica/complicações , Antígenos E da Hepatite B/uso terapêutico , Fosfatase Alcalina , DNA Viral , Estudos Retrospectivos , Fibrose , Vírus da Hepatite B/genética , Cirrose Hepática/etiologia , Inflamação/tratamento farmacológico , Antivirais/uso terapêutico , Alanina TransaminaseRESUMO
Objective:To analyze the liver pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and negative hepatitis B e antigen (HBeAg), and to evaluate the diagnostic value of different serological models for liver fibrosis.Methods:Retrospective analysis was conducted on the patients with HBeAg-negative CHB who had normal ALT and underwent liver biopsy from August 2016 to December 2019 in the Department of Infectious Diseases, Henan Provincial People′s Hospital. The clinical data, serum indicators of hepatitis B virus (HBV) and HBV DNA were collected. The liver fibrosis stages (S) was assessed by pathological examination. The diagnostic efficacies of gamma-glutamyl transpeptidase to platelet ratio (GPR), fibrosis 4 score (FIB-4), S index, aspartate aminotransferase to platelet ratio index (APRI) and gamma-glutamyl transpeptidase to albumin ratio (γ-GT/ALB) for liver pathological fibrosis were analyzed by the receiver operating characteristic curves. Two variable correlation test was used to explore the relationship between the different models and pathological fibrosis of liver tissue. Chi-square test was used for statistical comparison.Results:The age of 448 patients was (37.98±9.82) years, and the male to female ratio was 1.286 ∶1. The proportions of S≥2 in patients with age>30 years, hepatitis B surface antigen (HBsAg)<2 000 IU/mL and HBV DNA≥2 000 IU/mL were higher than those in patients with age ≤30 years, HBsAg ≥2 000 IU/mL and HBV DNA<2 000 IU/mL, respectively, and the differences were all statistically significant ( χ2=7.68, P=0.006; χ2=11.44, P=0.001; χ2=9.12, P=0.003, respectively). There were 250 cases with pathological fibrosis stage S<2, 162 cases with S=2 and 36 cases with S≥3. FIB-4 (correlation coefficient 0.250), APRI (correlation coefficient 0.218), GPR (correlation coefficient 0.186), S index (correlation coefficient 0.184) and γ-GT/ALB (correlation coefficient 0.127) were positively correlated with the severity of liver fibrosis (all P<0.050). S index had the highest sensitivity (64.1%) in the diagnosis of significant liver fibrosis (S≥2), while γ-GT/ALB had the highest specificity (80.8%). In the diagnosis of severe liver fibrosis (S≥3), γ-GT/ALB had the highest sensitivity (77.8%), while APRI had the highest specificity (78.6%). Conclusions:The incidence of liver fibrosis in CHB patients with normal ALT and negative HBeAg is relatively high. The current serological diagnostic models are not suitable for the evaluation of liver fibrosis in these patients, and timely liver puncture is still necessary.
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Objective:To establish a noninvasive prediction model for liver fibrosis in chronic hepatitis B (CHB) virus infection patients with alanine aminotransferase (ALT) less than upper limit of normal level.Methods:A total of 183 CHB patients with ALT <40 U/L admitted in the First Affiliated of Wenzhou Medical University from January 2014 to September 2017 were enrolled. There were 149 cases of non-marked liver fibrosis (F0-F2) and 34 cases of marked liver fibrosis (F3-F6) according to the Ishak scoring system. The clinical data, liver stiffness measurement (LSM), liver ultrasound imaging, serum biochemical features and hepatitis B virus related indexes of patients were retrospectively analyzed. The independent predictors of liver fibrosis were screened and a prediction model was constructed based on the results of multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was applied to evaluate the established model and other indicators in predicting liver fibrosis.Results:Multivariate logistic regression analysis showed that LSM ( OR=1.327, 95% CI 1.149-1.531), liver ultrasound scores ( OR=6.610, 95% CI 2.704-16.156) were independent predictors of liver fibrosis. The area under ROC curve(AUC)of the established model (LU) in predicting liver fibrosis was 0.873(95% CI 0.799-0.947), which was significantly greater than that of the ultrasound score, LSM, FIB-4, APRI and GPR (AUC=0.790, 0.804, 0.654, 0.673 and 0.770; Z=3.394, 1.982, 2.077, 3.168 and 2.165, all P<0.05 or <0.01). With the cut-off value of -1.787, the sensitivity and specificity of LU model were 85.3% and 77.2%, respectively. Conclusion:The established model (LU) can effectively predict the liver fibrosis in CHB patients with ALT less than upper limit of normal.
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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 investigate the correlation of liver stiffness measured by FibroTouch (FT) and FibroScan (FS) with Ishak fibrosis score in patients with chronic hepatitis B.@*Methods@#A total of 313 patients with chronic hepatitis B who visited Department of Liver Cirrhosis in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2014 to May 2016 were enrolled. All the patients underwent liver biopsy, and FT and FS were used to determine liver stiffness measurement (LSM). Serum biochemical parameters were measured, and the aspartate aminotransferase-to-platelet ratio index (APRI) in a multi-parameter model of liver fibrosis and fibrosis-4 (FIB-4) index were calculated. The consistency between the results of four noninvasive examinations and Ishak fibrosis score was compared. The t-test was used for comparison of LSM determined by FT and FS. Pearson correlation analysis was used investigate the correlation between LSM determined by FT and FS; Spearman correlation analysis was used to investigate the correlation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and Knodell score with LSM determined by FT and FS; the correlation between LSM determined by FT and FS and fibrosis stage was analyzed by partial correlation analysis adjusted by Knodell score for liver inflammatory activity; Spearman correlation analysis was used for APRI, FIB-4, and fibrosis stage. Based on the Ishak fibrosis score, the receiver operating characteristic (ROC) curve was used to analyze the values of four noninvasive methods in the diagnosis of liver fibrosis.@*Results@#There was no significant difference in LSM measured by FT and FS in all patients (15.75±9.42 kPa vs 15.42±10.52 kPa, P > 0.05) and Pearson correlation analysis indicated a significant positive correlation between them (r = 0.858, P < 0.01); serum ALT and AST levels and liver inflammatory activity were correlated with LSM determined by FT and FS. There was a significant positive correlation between LSM determined by FT and FS and fibrosis stage (r = 0.501 and 0.526, both P < 0.001), and APRI and FIB-4 were also positively correlated with fibrosis stage (r = 0.236 and 0.218, both P < 0.001). Based on the Ishak fibrosis score, in the diagnosis of fibrosis stages F3, F4, F5, and F6, the areas under the ROC curve were 0.915/0.856/0.839/0.816 for FT, 0.933/0.883/0.849/0.856 for FS, 0.618/0.630/0.608/0.638 for APRI, and 0.614/0.624/0.595/0.649 for FIB-4, and FT and FS had a significantly larger areas under the ROC curve than APRI and FIB-4.@*Conclusion@#LSM determined by FT or FS has a good correlation with the Ishak fibrosis score, so FT and FS have a significantly better diagnostic performance for liver fibrosis than APRI and FIB-4.
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Objective To analyze the relationship between intrahepatic expression of HBsAg and HBcAg and the serum HBsAg and the load of HBV DNA in low-level HBsAg.To provide the basis for the diagnosis of low-level HBsAg.Methods A total of 63 patients with HBsAg lower than 1 400 IU/mL and higher than 0.05 IU/mL were enrolled in the study.All the 63 patients with low level HBsAg were collected for liver biopsy from January 2013 to December 2015.Serum HBsAg was detected by Roche cobas e601 automatic electrochemiluminescence immunoas-say system and supporting reagents.HBV DNA was detected using ROCHE automatic AmpliPrep/cobas TaqMan 48 system detector and supporting reagents.Results Among the 63 patients,the HBsAg in liver tissue was negative in 5 cases(7.94%),+in 47 cases(74.60%),++in 8 cases(12.70%),+++in 2 cases(3.17%),and++++was found in 1 case.The expression of HBcAg were negative in 30 cases(47.62%),+in 28 cases(44.44%),++in 4 cases(6.35%),+++in 1 case(1.59%),and++++in 0 cases.There was a significant positive correlation between HBsAg expression and serum HBsAg level by spearman and kendall correlation analysis(spearman analysis:r = 0.261,P=0.039;kendall analysis:r=0.217,P=0.036).HBcAg expression was significantly correlated with serum HBV DNA load with spearman and kendall correlation analysis(spearman analysis:r=0.305,P=0.015;kendall analysis:r=0.259,P=0.017).Conclusions The expression of HBsAg in liver tissue of in the patients with low level of HBsAg is positively correlated with the level of serum HBsAg,but not with the load of HBV DNA. There is significant positive correlation between HBcAg expression and serum HBV DNA load.
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The present study was conducted to examine the biochemical and histopathological changes in liver of albino rats with oral sub-lethal (20 mg/kg) administration of chlorpyrifos as single, double and multiple doses with 48 hr intervals. Protease and glutamate dehydrogenase (GDH) enzyme activities increased in a dose and time dependent manner. Chlorpyrifos-induced histopathological changes included central venous congestion, sinusoidal haemorrhages, and focal necrotic areas in liver. Diffuse haemorrhagic areas were observed in the heart. Degenerative changes in the muscle layer, hypertrophy of goblet cells, and infiltration and hyperaemic changes in blood vessels were observed in the intestine. These results suggest that structural integrity of certain organ systems can be disrupted to a great extent from chlorpyrifos exposure.