INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping ...INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .展开更多
Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efifcacy of pegylated-interferon alfa-2a (Peg-IFN-α2a) in HBeAg-positive chronic hepatitis B (CHB) patients at w...Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efifcacy of pegylated-interferon alfa-2a (Peg-IFN-α2a) in HBeAg-positive chronic hepatitis B (CHB) patients at week 48 and to find a useful predictor for treatment efficacy and investigate individualized treatment of antiviral therapy. Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg who were treated with Peg-IFN-α2a were enrolled in this trial. They were categorized into 3 groups according to the changes of HBeAg in week 24:HBeAg decline>2 log10 group (group A), HBeAg decline between 1 1og10-2 log10 (group B), HBeAg decline<1 log10 group (group C), and group C was randomly distributed into C1 and C2. The patients in group A, group B, and group C1 continued the original therapy and the patients in group C2 were given lamivudine plus Peg-IFN-α2a for 24 weeks. At week 48, the treatment efifcacy and hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver biopsies were analyzed. Results At week 48, mean reduction of serum HBV DNA:group A:5.8 log10 copies/ml, group B:3.8 log10 copies/ml, group C1:2.8 log10 copies/ml, group C2:5.7 log10 copies/ml, the reduction of HBV DNA in group A was greater than groups B and C1 (P<0.01), that in group C1 was greater than group C2 (P<0.01), the difference between groups B and C1 had no statistical signiifcance (P=0.19). Mean reduction of HBeAg:group A:2.7 log10S/CO, group B:1.9 log10S/CO, group C1:0.9 log10S/CO, group C2:1.5 log10S/CO, the difference among groups A, B and C1 and between groups C1 and C2 were statistically signiifcant (P<0.01). At week 48, HBV DNA undetectable rate in group A, group B, group C1 and group C2 were 87.5%, 34.5%, 17.4%and 81.9%, respectively, the rate in group A was greater than groups B and C1 (P<0.01),that in group C1 was greater than group C2 (P<0.01). HBeAg seroconversion rate were 75.0%, 24.1%, 13.0%and 22.7%, respectively, that in group A was greater than groups B and C1 (P<0.01). Group A had lower cccDNA in liver tissue than group B and group C1 (P<0.01). The difference of HBV cccDNA between groups B and C1 and that between groups C1 and C2 had no statistical signiifcance. Conclusions HBeAg decline > 2 log10 at week 24 in Peg-IFN-α 2a-treated hepatitis B patients suggested a better efficacy at week 48; HBeAg decline < 2 log10 at week 24 suggests a worse efficacy at week 48, the combined therapy of Peg-IFN-α and lamivudine could improve the clinical responses. The change of quantitative of HBeAg at week 24 may be used as a predictor of treatment effects at week 48.展开更多
Background: We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens (HBcrAg) for predicting hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients...Background: We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens (HBcrAg) for predicting hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon (IFN) alfh-2b or pegylated IFN. Methods: Fifty-eight patients were enrolled: 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up (LTFU), during which time the dynamics of the HBcrAg was monitored. Results: The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group (from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were II0,245 kU/ml, 3760 kU/ ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively). HBcrAg 〈19,565 kU/ml at week 24, HBcrAg 〈34,225 kU/ml at 12-week follow-up, and HBcrAg decrease 〉0.565 log10 kU/ml from the baseline to the end of treatment (EOT) had negative predictive values (NPVs) of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values (PPVs) were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Conclusions: Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory (all 〈31%). The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.展开更多
Interleukins and intert-erons are distinct groups of cytokines that are upregulated after viral infection in humans and have been recogmzed as having antltumor activity. For example, high-dose interleukin-2 (IL-2) h...Interleukins and intert-erons are distinct groups of cytokines that are upregulated after viral infection in humans and have been recogmzed as having antltumor activity. For example, high-dose interleukin-2 (IL-2) has been used to treat malignant tumors, such as melanoma, in the clinic. In addition, interferon alfa-2b (IFNα-2b) has been applied extensively to treat hepatitis as well as renal cell carcinoma in the clinic.展开更多
Background: Hepatitis B surfhce antigen (HBsAg) Ioss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to as...Background: Hepatitis B surfhce antigen (HBsAg) Ioss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of ttBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a. Methods: A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (H BeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-1FN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. Results: Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3%, and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log 1U/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log I U/ml; t = 4.733, P 〈 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions: Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.展开更多
BACKGROUND The incidence of hepatocellular carcinoma(HCC)is high in China,and approximately 15%-20%of HCC cases occur in the absence of cirrhosis.Compared with patients with cirrhotic HCC,those with non-cirrhotic HCC ...BACKGROUND The incidence of hepatocellular carcinoma(HCC)is high in China,and approximately 15%-20%of HCC cases occur in the absence of cirrhosis.Compared with patients with cirrhotic HCC,those with non-cirrhotic HCC have longer postoperative tumor-free survival.However,the overall survival time is not significantly increased,and the risk of postoperative recurrence remains.Strategies to improve the postoperative survival rate in these patients are currently required.CASE SUMMARY A 47-year-old man with a family history of HCC was found to have hepatitis B virus(HBV)infection 25 years ago.In 2000,he was administered lamivudine for 2 years,and entecavir(ETV 0.5 mg)was administered in 2006.In October 2016,magnetic resonance imaging revealed a tumor in the liver(5.3 cm×5 cm×5 cm);no intraoperative hepatic and portal vein and bile duct tumor thrombi were found;and postoperative pathological examination confirmed a grade II HCC with no nodular cirrhosis(G1S3).ETV was continued,and no significant changes were observed on imaging.After receiving pegylated interferon alfa-2b(PEG IFNα-2b)(180μg)+ETV in February 2019,the HBsAg titer decreased significantly within 12 wk.After receiving hepatitis B vaccine(60μg)in 12 wk,HBsAg serological conversion was realized at 48 wk.During the treatment,no obvious adverse reactions were observed,except for early alanine aminotransferase flares.The reexamination results of liver pathology were G2S1,and reversal of liver fibrosis was achieved.CONCLUSION The therapeutic regimen of ETV+PEG IFNα-2b+hepatitis B vaccine for patients with HBV-associated non-cirrhotic HCC following hepatectomy can achieve an HBV clinical cure and prolong the recurrence-free survival.展开更多
基金This work was supported partly by Grant 90089102 from the Scientific Research Fund of the Ministry of Education,Japan
文摘INTRODUCTIONFrom the technical aspect of liver surgery ,control of bleeding during hepatic parenchymal resection is one of the most important procedures in hepatectomy .Pringle,s maneuver ,a temporary cross-clamping of the hepatoduodnal ligament ,has often been used for this purpose[1],This is the simplest and userul technique to reduce intraoperative blood loss .
文摘Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efifcacy of pegylated-interferon alfa-2a (Peg-IFN-α2a) in HBeAg-positive chronic hepatitis B (CHB) patients at week 48 and to find a useful predictor for treatment efficacy and investigate individualized treatment of antiviral therapy. Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg who were treated with Peg-IFN-α2a were enrolled in this trial. They were categorized into 3 groups according to the changes of HBeAg in week 24:HBeAg decline>2 log10 group (group A), HBeAg decline between 1 1og10-2 log10 (group B), HBeAg decline<1 log10 group (group C), and group C was randomly distributed into C1 and C2. The patients in group A, group B, and group C1 continued the original therapy and the patients in group C2 were given lamivudine plus Peg-IFN-α2a for 24 weeks. At week 48, the treatment efifcacy and hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver biopsies were analyzed. Results At week 48, mean reduction of serum HBV DNA:group A:5.8 log10 copies/ml, group B:3.8 log10 copies/ml, group C1:2.8 log10 copies/ml, group C2:5.7 log10 copies/ml, the reduction of HBV DNA in group A was greater than groups B and C1 (P<0.01), that in group C1 was greater than group C2 (P<0.01), the difference between groups B and C1 had no statistical signiifcance (P=0.19). Mean reduction of HBeAg:group A:2.7 log10S/CO, group B:1.9 log10S/CO, group C1:0.9 log10S/CO, group C2:1.5 log10S/CO, the difference among groups A, B and C1 and between groups C1 and C2 were statistically signiifcant (P<0.01). At week 48, HBV DNA undetectable rate in group A, group B, group C1 and group C2 were 87.5%, 34.5%, 17.4%and 81.9%, respectively, the rate in group A was greater than groups B and C1 (P<0.01),that in group C1 was greater than group C2 (P<0.01). HBeAg seroconversion rate were 75.0%, 24.1%, 13.0%and 22.7%, respectively, that in group A was greater than groups B and C1 (P<0.01). Group A had lower cccDNA in liver tissue than group B and group C1 (P<0.01). The difference of HBV cccDNA between groups B and C1 and that between groups C1 and C2 had no statistical signiifcance. Conclusions HBeAg decline > 2 log10 at week 24 in Peg-IFN-α 2a-treated hepatitis B patients suggested a better efficacy at week 48; HBeAg decline < 2 log10 at week 24 suggests a worse efficacy at week 48, the combined therapy of Peg-IFN-α and lamivudine could improve the clinical responses. The change of quantitative of HBeAg at week 24 may be used as a predictor of treatment effects at week 48.
文摘Background: We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens (HBcrAg) for predicting hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon (IFN) alfh-2b or pegylated IFN. Methods: Fifty-eight patients were enrolled: 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up (LTFU), during which time the dynamics of the HBcrAg was monitored. Results: The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group (from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were II0,245 kU/ml, 3760 kU/ ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively). HBcrAg 〈19,565 kU/ml at week 24, HBcrAg 〈34,225 kU/ml at 12-week follow-up, and HBcrAg decrease 〉0.565 log10 kU/ml from the baseline to the end of treatment (EOT) had negative predictive values (NPVs) of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values (PPVs) were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Conclusions: Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory (all 〈31%). The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.
文摘Interleukins and intert-erons are distinct groups of cytokines that are upregulated after viral infection in humans and have been recogmzed as having antltumor activity. For example, high-dose interleukin-2 (IL-2) has been used to treat malignant tumors, such as melanoma, in the clinic. In addition, interferon alfa-2b (IFNα-2b) has been applied extensively to treat hepatitis as well as renal cell carcinoma in the clinic.
文摘Background: Hepatitis B surfhce antigen (HBsAg) Ioss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of ttBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a. Methods: A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (H BeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-1FN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. Results: Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3%, and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log 1U/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log I U/ml; t = 4.733, P 〈 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. Conclusions: Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.
基金Natural Science Foundation of Fujian Province,No.2019J01593High-Level Talent Innovation Project of Quanzhou,No.2018C067R+2 种基金Science and Technology Innovation Joint Project of Fujian Province,No.2019Y9048Youth Research Project of Fujian Provincial Health Commission,No.2018-1-94 and No.2018-1-95Science and Technology Project of Quanzhou,No.2018Z074 and No.2018Z069.
文摘BACKGROUND The incidence of hepatocellular carcinoma(HCC)is high in China,and approximately 15%-20%of HCC cases occur in the absence of cirrhosis.Compared with patients with cirrhotic HCC,those with non-cirrhotic HCC have longer postoperative tumor-free survival.However,the overall survival time is not significantly increased,and the risk of postoperative recurrence remains.Strategies to improve the postoperative survival rate in these patients are currently required.CASE SUMMARY A 47-year-old man with a family history of HCC was found to have hepatitis B virus(HBV)infection 25 years ago.In 2000,he was administered lamivudine for 2 years,and entecavir(ETV 0.5 mg)was administered in 2006.In October 2016,magnetic resonance imaging revealed a tumor in the liver(5.3 cm×5 cm×5 cm);no intraoperative hepatic and portal vein and bile duct tumor thrombi were found;and postoperative pathological examination confirmed a grade II HCC with no nodular cirrhosis(G1S3).ETV was continued,and no significant changes were observed on imaging.After receiving pegylated interferon alfa-2b(PEG IFNα-2b)(180μg)+ETV in February 2019,the HBsAg titer decreased significantly within 12 wk.After receiving hepatitis B vaccine(60μg)in 12 wk,HBsAg serological conversion was realized at 48 wk.During the treatment,no obvious adverse reactions were observed,except for early alanine aminotransferase flares.The reexamination results of liver pathology were G2S1,and reversal of liver fibrosis was achieved.CONCLUSION The therapeutic regimen of ETV+PEG IFNα-2b+hepatitis B vaccine for patients with HBV-associated non-cirrhotic HCC following hepatectomy can achieve an HBV clinical cure and prolong the recurrence-free survival.