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ObjectiveTo investigate the diagnostic efficacy and optimal cut-off values of alpha-fetoprotein （AFP） and alpha-fetoprotein variant L3 （AFP-L3） in hepatitis B virus （HBV）-related early-stage hepatocellular carcinoma （HCC）. MethodsA total of 1 080 patients with HBV-related HCC （HBV-HCC） who were diagnosed for the first time and not yet treated in The Third Affiliated Hospital of Sun Yat-Sen University from January 2019 to July 2022 were enrolled as HCC group in the study， among whom there were 620 patients with CNLC Ⅰa-Ⅱa HCC， and in addition， 346 patients with HBV-related chronic hepatitis B （CHB group） and 293 patients with HBV-related liver cirrhosis （LC group） were enrolled as controls. The diagnostic efficacy of AFP and AFP-L3% in screening for HBV-related early-stage HCC was analyzed， including sensitivity， specificity， and the area under the ROC curve （AUC）. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni method was used for further comparison between two groups. ResultsThe HCC group had significantly higher levels of AFP and AFP-L3% than the CHB group and the LC group （H=542.479 and 418.974， both P<0.001）. In early-stage HCC， AFP and AFP-L3% had an optimal cut-off value of 8.7 ng/mL and 5%， respectively， and AFP alone had the largest AUC of 0.816， with a sensitivity of 66.9% and a specificity of 85.1%. There was no significant difference in AUC between AFP-L3%+AFP and AFP alone （Z=0.609， P=0.543）， but both AFP-L3%+AFP and AFP alone had a significantly larger AUC than AFP-L3% alone （AFP vs AFP-L3%： Z=8.173， P<0.001； AFP+AFP-L3% vs AFP-L3%： Z=8.802， P<0.001）. ConclusionAFP has a good value and is superior to AFP-L3% in the diagnosis of HBV-related early-stage HCC， and the screening cut-off value of AFP should be lowered in order to improve the detection rate of early-stage HCC.
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Objective@#To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks.@*Methods@#Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman’s rank correlation coefficient was used to test bivariate associations.@*Results@#Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29).@*Conclusion@#Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.
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Objective To evaluate the influence of Fuzheng Huayu decoction on different pathological stages fibrotic liver tissue and activated hepatic stellate cells (HSCs). Methods Use a carbon tetrachloride (CCl4)-induced liver cirrhosis rat model system. The drug intervention was administered via oral-gastric irrigation in building, the end of week 2 and 4. Rats were batch sacrificed at the end of week 2 , 4, and 6. Liver fibrosis was evaluated by histology, and expression of a-smooth muscle actin (α-SMA) was determined by immunohistochemistry. Between-group comparisons were made by completely random design and ANOVA with Bonferroni correction. Results At the end of weeks 2, 4 and 6, the model group and drug intervention groups had significantly higher area ratio of liver fibrosis and higher expression of α-SMA than the normal group, but the three drug intervention groups had significantly less area ratio of liver fibrosis and less expression of α-SMA than the model group and the drug intervention 1 group showed the most robust decrease (P<0.05). Conclusion The Fuzheng Huayu decoction leads to down-regulated α-SMA expression and reduced degree of liver fibrosis on different pathological stages of fibrotic liver tissue, and the earlier drug intervention, the better the results.
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Objective To assess the application of a new scoring system for severity evaluation of acute-on-chronic liver failure induced by hepatitis B.Methods A total of 399 patients (203 survivals and 196 deaths) with acute-on-chronic liver failure induced by hepatitis B were collected from the Third Affiliated Hospital of Sun Yat-sen University during January 2003 and June 2008.All patients were graded with the new scoring system and model for end-stage liver disease (MELD) at critical stage (survivals) or terminal stage (deaths).The survival rates and fatality rates of patients who were graded by two scoring systems were analyzed and compared.Results With MELD system,the fatality rate was 11.89％ (17/143) in patients with scores of 15-26,64.68％ (141/218) with scores of 27-48,and 100％ (38/38) with scores of 49-69.No score range with fatality rate of 0 was found.While with the new scoring system,the survival rate was 99.2％ (126/127) when the severity scores were between 2 to 8,and patients with scores 2,3,4,5,6 and 8 were all survived; the fatality rates were gradually raised from 4.2％ (1/24) with scores of 9-17 to 100％ (82/82) with scores of 18 and above.Conclusion The new scoring system is more objective,simple and sensitive than MELD system,which can be used for severity evaluation of acute-onchronic liver failure induced by hepatitis B.
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Objective To evaluate the effects of nucleoside/nucleotide analogue treatment on immunoglobulin and complement in patients with chronic hepatitis B (CHB).MethodsA total of 157 CHB patients were recruited and divided into CHB group,liver cirrhosis (LC) group and severe hepatitis B (SHB) group.There were 50 patients who received oral antiviral treatment (lamivudine 100 mg/d,or entecavir 0.5 mg/d,or telbivudine 600 mg/d).Serum levels of complement 3 and 4 (C3,C4),C-reaction protein (CRP),hemolytic complement (CH50),immunoglobulin G,M,A (IgG,IgM,IgA),hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were detected by enzyme-linked immunosorbent assay (ELISA) or immunoturbidimetry.Hepatitis B virus (HBV) DNA was quantified by real-time polymerase chain reaction (RT-PCR) before and 1,2,3 and 4 weeks after nucleoside antiviral therapy.Comparison of means was done by t test and Mann-Whitney test.The correlation was analyzed by Pearson correlation coefficient test.ResultsSerum IgA and IgM levels of SHB and LC patients were significantly higher than those of CHB patients (P＜0.01).Levels of C3,C4,CH50 and CRP were significantly different among three groups.Levels of C3,IgM,IgG and HBV DNA in HBeAg positive patients were significantly different from those in HBeAg negative patients.There was a statistically significant difference of IgA,IgM,C3 and CH50 levels between patients with high HBV DNA level and low HBV DNA level in HBeAg-positive patients.While in the HBeAg-negative patients,only the IgA level was significantly different with HBV DNA levels.After anti-viral treatment,immunoglobulin and HBV DNA levels were all decreased in three groups,while the serum complement level was increased compared to baseline,and the differences became significant at week 4 of treatment. HBV DNA level was negatively correlated with C3 (r=-0.78,P=0.021) and HBeAg titer was positively correlated with C3 (r=0.87,P=0.015).ConclusionsThe immunoglobulin,CRP,C3,C4,and C H50 could reflect the inflammatory activity in liver.The changes of C3 level can predict the efficacy of antiviral therapy.
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Objective To investigate the relationship between serum levels of alanine aminotransferase (ALT)or aspartate aminotransferase (AST)apportioned by the same hepatic parenchyma cell volume and liver histological necroinflammation grades in HBeAg-negative chronic hepatitis B (CHB)patients.Methods A total of 145 CHB patients were divided into four groups:Gl,G2,G3 and G4 based on the liver histological necroinflammation grade.The serum ALT and AST levels were determined by automatic biochemical instrument in these four groups.Furthermore,serum ALT and AST levels were then apportioned by the same hepatic parenchyma cell volume.The data were analyzed by ANOVA.Results Mean serum ALT levels in G1,G2,G3 and G4 groups were (35.3±29.1),(91.6±120.4),(111.6± 116.1)and (118.0±122.1)U/L,respectively,and the serum ALT levels apportioned by same hepatic parenchyma cell volume were ( 54.0 ± 45.1 ),( 144.2 ± 184.9 ),(191.3± 204.8)and (215.1 ± 226.5)U/L,respectively.The pairwise comparison between G1 and other three groups all showed statistically significant difference (P＜0.05).Meanwhile,AST levels in G1 to G4 groups were (35.5± 29.0),(64.9±71.7),(96.0±81.9)and (102.8±77.0)U/L,respectively and the serum AST levels apportioned by the same hepatic parenchyma cell volume were (54.3±44.6),(102.3± 107.9),(165.2±148.7)and (189.4±145.4)U/L,respectively.The pairwise comparison between G1 and G3,G1 and G4,G2 and G3,G2 and G4 all showed statistically significant difference (P＜0.05).Conclusion Both AST and ALT levels are sensitive indicators for liver inflammation grading in HBeAg-negative CHB patients during the natural history of the disease.
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Objective To investigate the risk factors of hepatitis B virus(HBV) re-infection after orthotopic liver transplantation(OLT)and to evaluate the therapeutic efficacy of hepatitis B immunoglobulin(HBIG)combined with nucleos(t)ide analogues. Methods The study included 160 patients with HBVrelated liver diseases who underwent OLT in the Third Affiliated Hospital of Sun Yat-sen University from October 2003 to Augest 2007, 117 of whom were treated with nucleos(t)ide analogues before OLT;and all patients were received HBIG i. m and nucleos(t)ide analogues treatment after OLT. Preoperative data of the patients were retrospectively reviewed, and HBV re-infection was assessed prospectively. Independent t test was used to compare normally distributed data and Fisher's exact test was used for the comparison of rates among groups. Results HBV re-infection Was observed in 19 patients after OLT with a rate of 11. 88%(19/160), which was not correlated with HBV DNA loads, HBeAg and the duration of antiviral therapy before OLT(r=0.108, 0.127 and 0.033, P>0.05). Of 19 patients with HBV re-infection, 17 were treated with lamivudine after OLT, and HBV YMDD mutants were detected in 8. The YMDD positive group had a higher HBV DNA level than YMDD negative group(7.0 ± 2.0 log copies/mL vs 3.2 ± 2.5 log copies/mL, t = 3.531, P=0.003). Among above 17 patients, 12 received adefovir add-on treatment, and3 received entecavir instead of lamivadine; all achieved satisfactory responses. Conclusions Low dose of HBIG combined with long-term use of nucleos(t)ide analogues can effectively prevent HBV re-infection after OLT. HBV YMDD mutation may be the primary reason for HBV re-infection in the patients treated with lamivudine after OLT.
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Objective To establish a scoring system for evaluating the severity of hepatitis B patients with acute-on-chronic liver failure and to compare the validity of this system with model for end-stage liver disease (MELD). Methods MELD score was used in hepatitis B patients with acuteon-chronic liver failure who were divided into survival group (203 cases) and death group (196 cases).Seven clinical relative indices, including prothrombin activity, serum creatinine, hepatic encephalopathy, accompanying infections, serum total bilirubin, the dimension of liver, the amount of ascites, were selected for evaluating the severity. Each index was graded with 1 to 4 points based on the severity. Then the total score was counted by adding up scores of each index. T test and area under receiver operating characteristic (ROC) were used to evaluate the difference and similarity of the two systems. Results According to the new scoring system, the total score was 8. 07±3. 14 in the survival group and 16. 91 ±3. 54 in the death group. There was a statistically significant difference between these two groups (t = 26.125. P<0.01). In 81.32% of survival patients, their scores ranged from 3.91 to 12.23, while in 81.32% of dead patients, their scores ranged from 12.23 to 21.60. The two ranges overlapped at 12.23. According to the MELD system, the total score was 26. 43 ±5. 58 in the survival group and 40. 16 ±10. 22 in the death group. The difference between the two groups was statistically different (t = 16. 566, P<0. 01). In 61.02% of survival patients, the MELD scores ranged from 21. 49 to 31. 19, while in 61. 02% of the dead patients, the MELD scores ranged from 31. 19 to 48. 94. The two ranges overlapped at 31.19. The areas under ROC of the new scoring system and MELD system were 0.960 (95% CI: 0. 944-0. 977) and 0.886 (95% C/;0. 852 - 0. 920). No overlap was found in these two 95%CJ and there was a statistically significant difference. Conclusions The new scoring system is applicable for evaluating the severity and prognosis of acute-on-chronic liver failure in hepatitis B patients. The sensitivity of this new scoring system is approximate to the MELD system.
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Objective To investigate the susceptibility of bone marrow mesenchymal stem cell (BMSC) to hepatitis B virus (HBV) infection during induction toward hepatocyte and the role of asialoglycoprotein receptor (ASGPR) in BMSC HBV infection. Methods BMSC obtained from hepatitis B patients were tested for HBV infection and then cultured with HBV infectious serum in vitro and induced to differentiate into hepatocyte through exposure to hepatocyte growth factor (HGF), fibroblast growth factor-4(FGF-4), and epidermal growth factor(EGF). Subsequently these cells were determined for the presence of hepatitis B virus e antigen( HBeAg), hepatitis B virus surface antigen(HBsAg) and ASGPR. All experiments were repeated for 3 times in 5 different samples. The results were analyzed by non-parametric test. Results After 6 days of exposure, BMSC-derived hepatocyte-like cells expressed hepatic special genes and proteins, including alpha fetoprotein(AFP),cytokeratin18 (CK18), albumin (Alb), and manifested hepatocyte functions, including glycogen synthesis, urea secretion and albumin synthesis. Expressions of CK18 and Alb were increased, and AFP was decreased with time of induction. The BMSC were resistant to HBV infection both in vitro and in vivo or after induction toward hepatocyte. ASGPR expression level was low in BMSC, which was increased in the induced BMSC but still lower than that of the control HepG2 cells. Conclusions BMSC are resistant to HBV infection both in vitro and in vivo. The low level expression of ASGPR may be a reason for this.
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Objective To evaluate the long-term prognosis of patients with HBV-related decompensated cirrhosis after treatment with nucleos (t) ide analogues. Methods Totally 94 patients with HBV-related decompensated cirrhosis were enrolled, 53 in nucleos(t) ide group, 41 in control group, and both received routine treatments. Patients in nucleos (t)ide analogue group also received lamivudine ( 100 mg/d), or adefovir ( 10 mg/d), or entecavir (0.5 rag/d). The follow-up was terminated for those who developed hepatocellular carcinoma, received liver transplantation, died or refused the treatment. Serum biochemical markers, Child-Pugh grades and clinical outcomes were compared between two groups at the end of following up. Results After nucleos (t) ide analogues therapy, ALT, AST, globulin ( Glb), and TBil decreased, while Alb and cholinesterase (CHE) increased in the nucleos(t)ide group, and Chiid-Pugh scores decreased in 43 (81.1%) patients. While in the control group, ALT, AST, Glb and TBil did not show significant changes, but the CHE was significantly lower than before ( t = 5. 225, P < 0. 01 ). More patients in nucleos (t)ide group showed improvements in Child-Pugh grades, and there was significant difference between the two groups (X2 = 52.16, P <0.01). The incidence of HCC is lower in nucleos(t) ide group (0%) than that in the control group ( 19.5% ) ( X2 = 23.07, P < 0.01 ). The incidence of death and liver transplantation between two groups did not show siguificant difference. Conclusions Nucleos(t) ide analogues therapy can significantly improve biochemical status of liver functions in patients with HBV-related decompensated cirrhosis. The incidence of hepatocellular carcinoma may decline and the long-term prognosis can be improved.