Relationship between serum HBV DNA level and follicular helper T lymphocyte in patients with chronic hepatitis B and its significance / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore relationship between HBV DNA level and peripheral blood follicular helper T lymphocyte (Tfh) in patients with chronic hepatitis B (CHB) and its significance.</p><p><b>METHODS</b>HBV DNA levels of 179 cases of CHB patients with positive HBV DNA, positive HBeAg and positive human leukocyte antigen(HLA)-A2 were tested with real time fluorescent quantitative PCR. Tfh and HBV specific CTL were tested with flow cytometry. IL-21 was also tested. 179 cases of CHB patients were divided into group A and group B based on HBV DNA levels, 86 cases in group A, HBV DNA levels were 10(4)-10(5) copies/ml, 93 cases in group B, HBV DNA levels were 10(6)-10(7) copies/ml. Above testing indexes of the two groups were compared.</p><p><b>RESULTS</b>HBV DNA levels of group A were (4.85 +/- 0.37) log10 copies/ml, HBV DNA levels of group B were (6.83 +/- 0.31 ) log10 copies/ml, t = 27.31, P < 0. 001; Tfh of group A was (5.96 +/- 1.59)%, higher than that of group B (3.71 +/- 2.15)%, t = 4.92, P < 0.01; IL-21 of group A was (42.61 +/- 15.11)ng/L, higher than that of group B (14.91 +/- 3.15) ng/L, t = 8.62, P < 0.01; HBV specific CTL of group A was (0.36 +/- 0.08)%, higher than that of group B (0.18 +/- 0.06)%, t = 19.99, P < 0.001.</p><p><b>CONCLUSION</b>Serum HBV DNA level of CHB patients is related to the level of peripheral blood Tfh level: patients with low HBV DNA level have high Tfh level, high IL-21 level and high HBV specific CTL level. Patients with high HBV DNA level have low Tfh level, low IL-21 level and low HBV specific CTL level. The mechanism of baseline HBV DNA level affecting anti-viral therapy may be related to Tfh level.</p>

Effect of kurarinol on peripheral blood CTL surface PD-1 expression of patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the anti-viral mechanism of kurarinol through studying its influence on cytotoxic T lymphocyte (CTL) surface program death receptor-1 (PD-1) expression of patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>69 cases of CHB, HBV DNA > or = 10(4) copies/ml, HBeAg positive, human leukocyte antigen (HLA)-A2 positive, alanine aminotransferase (ALT) > 2 x upper limit of normal value(ULN).69 cases were randomly divided into two groups:34 cases in treatment group,600 mg of kurarinol glucose injection was used for intravenous dripping, once a day, one month later, 200 mg of kurarinol capsule was used orally,three times a day and 200 mg of silybin meglumine tablet was used orally, three times a day. 35 cases in control group, only silibin meglumine tablet was used, method and dosage were the same as those of treatment group. Three months later, their peripheral blood HBV specific CTL surface PD-1 expression, non-specific CTL surface PD-1 expression and level of HBV specific CTL,HBV DNA and HBeAg negative rate and liver functions were analyzed and compared.</p><p><b>RESULTS</b>3 months after treatment, peripheral blood HBV specific CTL surface PD-1 expression of the treatment group decreased compared with that before treatment (t = 2.39, P < 0.05), it also decreased compared with that of the control group 3 months after treatment (t = 2.26, P < 0.05), HBV specific CTL increased compared with that before treatment( t = 3.01, P < 0.01), it also increased compared with that of the control group after treatment (t = 2.65, P < 0.05). There was no significant difference of non-specific CTL surface PD-1 expression compared with that before treatment (P > 0.05), and there was no significant difference compared with that of the control group after treatment (P > 0.05). HBV DNA of 11 cases (32.5%) turned negative ( HBV DNA < 500 copies/ ml), higher than that of the control group after treatment (2 cases, 5.71%) chi2 = 7.99, P < 0.01, HBeAg of 9 cases (26.47%) turned negative, higher than that of the control group after treatment (1 case, 2.86%), chi2 = 7.75, P < 0.01.</p><p><b>CONCLUSION</b>Kurarinol can increase level of HBV specific CTL by down-regulating peripheral blood HBV specific CTL surface PD-1 expression of CHB patients, which may be one of the possible mechanisms that kurarinol can remove or inhibit HBV of CHB patients.</p>

Relationship between viral genotype and specific and nonspecific CTL of patients with cirrhotic hepatitis B and its significance / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore relationship between different HBV genotypes and peripheral blood HBV specific and nonspecific CTL of patients with cirrhotic hepatitis B and its significance.</p><p><b>METHODS</b>HBV genotypes were tested in 91 patients with cirrhotic hepatitis B, differences of HBV specific and nonspecific CTL between patients infected with genotype B and C were compared and its significance was explored.</p><p><b>RESULTS</b>In 91 cases of cirrhotic hepatitis B, 55 cases (60.44%) belong to genotype C, 35 cases (38.46%) belong to genotype B, 1 case (1.1%) belongs to mixture genotype B and C. In genotype C, 27 cases (49.09%) had positive (HLA)-A2, HBV specific CTL was 0.18% +/- 0.03%. In genotype B, 18 cases (51.43%) had positive HLA-A2, HBV specific CTL was 0.38% +/- 0.04%, higher than that in genotype C, t = 5.01, P < 0.01. Nonspecific CTL: genotype C (11.87% +/- 1.50%); genotype B (11.90% +/- 1.51%), t = 0.14, P < 0.05. HBV DNA level: genotype C (6.01 +/- 0.81) log10 copy/ml, higher than that in genotype B (5.01 +/- 0.54) log10 copy/ml, t = 5.01, P < 0.01. ALT: genotype C (251.13 +/- 131.11) U/L, higher than that in genotype B (121.25 +/- 63.21) U/L, t = 3.61, P < 0.01. TBil (45.61 +/- 15.11) micromol/L, higher than that in genotype B (28.11 +/- 6.25) micromol/L, t = 3.05, P < 0.01.</p><p><b>CONCLUSION</b>Compared with patients infected with genotype B of cirrhotic hepatitis B, HBV specific CTL of patients infected with genotype C was lower, resulting in higher level of HBV DNA and more severe damage of liver function.</p>

Association of serum HBV DNA level with cytotoxic T lymphocytes in patients with HBV-induced hepatic cirrhosis / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the association of serum HBV DNA level with HBV-specific and nonspecific cytotoxic T lymphocytes (CTL) in patients with HBV-induced hepatic cirrhosis.</p><p><b>METHODS</b>120 patients with HBV-induced hepatic cirrhosis who were positive for HBV DNA, HBeAg and human leucocyte antigen (HLA)-A2 were enrolled in this study. The level of HBV DNA was determined by real time fluorescence quantitative polymerase chain reaction (PCR). HBV-specific and nonspecific CTL were detected by flow cytometry. Liver function tests were done in the 120 patients. The 120 patients were divided into group A and B based on their HBV DNA levels. In group A, there were 68 patients with HBV DNA level of 3-4 log10 copy/ml, and in group B, 52 with 5-6 log10 copy/ml. HBV-specific and nonspecific CTL and liver function were compared between the two groups.</p><p><b>RESULTS</b>HBV DNA levels were (3.68 +/- 0.19) and (5.97 +/- 0.32) log10 copy/ml in Group A and B respectively with P < 0.001. HBV-specific CTL was higher in group A (0.33% +/- 0.04%) than in group B (0.11% +/- 0.01%) with P < 0.001. HBV-nonspecific CTL were (11.99% +/- 1.51% ) and (11.91% +/- 1.61%) in group A and B respectively with P > 0. 05.</p><p><b>CONCLUSION</b>The level of serum HBV DNA is related to the levels of HBV-specific CTL in patients with HBV-induced hepatic cirrhosis. Patients with higher HBV DNA had lower levels of HBV-specific CTL, and the damage to liver function was severe because of higher levels of HBV DNA. Patients with lower HBV DNA had higher levels of HBV-specific CTL which predict good anti-viral effect.</p>

Effect of medical ozone therapy on renal blood flow and renal function of patients with chronic severe hepatitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Medical ozone therapy system was reported to have certain effects on the treatment of severe hepatitis, but its mechanism is not very clear. One of the causes of death of severe hepatitis is complication of renal damage or hepatorenal syndrome. The present study aimed to observe effects of medical ozone therapy system on plasma renin activity (PRA), angiotensin II (AII), aldosterone (ALD), renal blood flow and renal function of patients with chronic severe hepatitis and explore mechanisms of medical ozone therapy in the treatment of severe hepatitis.</p><p><b>METHODS</b>Eighty-five cases with chronic severe hepatitis were randomly divided into ozone therapy group (43 cases) and control group (42 cases). The patients in the ozone therapy group were treated with basic treatments plus ozone therapy system. Basic autohemotherapy was used. One hundred milliliter venous blood was drawn from each patient, and was mixed with 100 ml (35 µg/ml) medical ozone and then was returned the blood to the patient intravenously, once every other day for 20 days. Only the basic treatments were given to the control group. PRA, AII, ALD, renal blood flow and damage to renal function of the two groups before treatment and 20 days after treatment were compared. Survival rates were also compared.</p><p><b>RESULTS</b>Twenty days after the treatment, in ozone therapy group, PRA was (1.31 ± 0.12) ng·ml⁻¹·h⁻¹, AII (111.25 ± 17.35) pg/ml, ALD (251.31 ± 22.60) pg/ml, which decreased significantly compared with those before treatment (PRA (2.23 ± 0.13) ng·ml⁻¹·h⁻¹, AII (155.18 ± 19.13) pg/ml, ALD (405.31 ± 29.88) pg/ml, t = 4.67 - 14.23, P < 0.01), also lower than those of control group 20 days after the treatment (PRA (2.02 ± 0.11) ng·ml⁻¹·h⁻¹, AII (162.21 ± 15.32) pg/ml, ALD (401.20 ± 35.02) pg/ml, t = 4.97 - 15.61, P < 0.01); renal blood flow was (175.15 ± 28.20) ml/min, which increased compared with that before the treatment ((125.68 ± 21.25) ml/min) and was higher than that of control group 20 days after the treatment ((128.59 ± 23.15) ml/min, t = 4.78, 4.61, P < 0.01). Renal damage occurred in 2 cases (5%) in ozone therapy group, less than that in control group (9 cases, 21%) (χ² = 5.295, P < 0.05). Thirty-three cases (77%) in ozone therapy group vs. 16 cases (38%) in control group survived (χ² = 12.993, P < 0.01).</p><p><b>CONCLUSIONS</b>Basic treatment plus medical ozone therapy for patients with chronic severe hepatitis could decrease PRA, AII and ALD levels significantly increase renal blood flow, prevent renal damage to certain extent and improve survival rate of the patients.</p>

Influence of Kurarinol on specific and non-specific cell immunity in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore influence of Kurarinol on specific and non-specific cell immunity in patients with chronic hepatitis B.</p><p><b>METHODS</b>74 cases of CHB were randomly divided into two groups, 36 cases in treatment group, treated with 600 mg Kurarinol glucose injection, IV, once a day. After one month, Kurarinol capsule was used orally, three times a day for 2 months, 200 mg Silybin Meglumine Tablets orally, three times a day for 3 months. 38 cases in control group, only Silybin Meglumine Tablets was used, method and dosage were the same as treatment group. Compare HBV specific CTL, non-specific CTL, sub-group of T cells, changes of Th1 and Th2, negative conversion rate of HBV DNA and HBeAg of the two groups.</p><p><b>RESULTS</b>In treatment group, 3 months after treatment with Kurarinol, HBV specific CTL is higher than that before treatment (P < 0.01), it is also higher than that of control after treatment, P < 0.05) . Non-specific CTL is higher than that before treatment (P < 0.05), it is also higher than that of control after treatment (P < 0.01). CD4 is higher than that before treatment (P <0.05), it is also higher than that of control after treatment (P < 0.01), Thl is higher than that before treatment (P < 0.05), it is also higher than that of control after treatment (P < 0.01) . Negative conversion of HBV DNA and HBeAg is higher than that of control (P < 0.01).</p><p><b>CONCLUSION</b>Kurarinol can improve specific and non-specific cell immunity in patients with CHB. It is one of the mechanisms that Kurarinol can clear or inhibit HBV of patients with CHB.</p>

Relations between ALT level and count of HBV special CTL and non-specific CTL in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore relations between ALT level and hepatitis B virus (HBV) specific CTL and non-specific CTL in patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>148 cases of CHB were divided into three groups according to ALT level. 35 cases in group A, ALT > or =2 x upper limit of normal value (ULN)--5 x ULN (100-250 IU/L); 53 cases in group B, ALT > 5 x ULN-- < or =10 x ULN (251-500 IU/L); 60 cases in group C, ALT > 10 x ULN ( > 500 IU/L). Flow cytometry is used to determine non-specific CTV. HBV specific CTL was tested on 74 cases of CHB (17 in group A, 27 in group B and 30 in group C) with positive (HLA)-A2. Compare HBV specific CTL, non-specific CTL, HBV DNA levels and positive rate of HBeAg.</p><p><b>RESULTS</b>HBV specific CTL: Group A (0.42 +/- 0.10)% is higher than group B (0.25 +/- 0.08)%, t = 6.37, P < 0.01, group B is higher than group C (0.17 +/- 0.004)%, t = 5.14, P < 0.01; Non-specific CTL: Group A (15.01 +/- 3.01)% is lower than group B (18.1 +/- 5.02)%, t = 2.81, P < 0.01, group B is lower than group C (21.5 +/- 6.11)%, t = 3.07, P < 0.01; HBV DNA level: Group A [(4.97 +/- 0.86) log10 copies/ml] is lower than group B [(5.92 +/- 0.92) log10 copies/ml], t = 4.87, P < 0.01. Group B is lower than group C [(6.37 +/- 0.71) log10 copies/ml], t = 2.92, P < 0.01; Positive HBeAg: Group A (15 cases, 42.86%) is lower than group B (32 cases, 60.38%), chi2 = 2.59, P > 0.05. Group B is lower than group C (41 cases, 68.33%), chi2 = 0.78, P > 0.05. Group A is lower than group C, chi2 = 5.929, P < 0.05.</p><p><b>CONCLUSION</b>The higher the non-specific CTL of patients with CHB is, the higher the ALT level would be, whereas the lower the HBV specific CTL is, the stronger the HBV replication would be.</p>

Relationship between serum HBV DNA level and HBV-specific, nonspecific cytotoxic T lymphocytes and natural killer cells in patients with chronic hepatitis B / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The response of patients with chronic hepatitis B (CHB) to antiviral therapy against hepatitis B virus (HBV) is related to the base line level of HBV DNA, but the mechanism is not clear. The present study aimed to understand the possible relationship between the level of HBV DNA and HBV-specific, nonspecific cytotoxic T lymphocytes (CTL) and natural killer (NK) cells of CHB patients and the mechanism how the HBV DNA level influences the antiviral therapeutic effect.</p><p><b>METHODS</b>Totally 100 adult patients with CHB who were positive for HBV DNA, HBeAg and (HLA)-A2 were enrolled into this study. HBV DNA was tested by real time fluorescence quantitative polymerase chain reaction (PCR). HBV specific and nonspecific CTL and NK cells were tested by flowcytometry. Serum alanine aminotransferase (ALT) and total bilirubin (TBil) were determined for each patient using routine biochemical tests. The 100 cases were assigned to two groups based on their HBV DNA level: group A had 48 cases, their HBV DNA level was 10(4) - 10(5) copies/ml, group B had 52 cases, their HBV DNA level was 10(6) - 10(7) copies/ml. HBV specific CTL, nonspecific CTL, NK cells, ALT and TBil of the two groups were compared.</p><p><b>RESULTS</b>HBV DNA level of groups A and B was (4.81 +/- 0.39) log(10) copies/ml and (6.81 +/- 0.40) log(10) copies/ml, respectively (t = 25.32, P < 0.001). HBV specific CTL and NK cells of group A were significantly higher than those of group B (P < 0.001 for both). Nonspecific CTL of group A was significantly lower than that of group B (P < 0.01). ALT and TBil of group A were significantly lower than those of group B (P < 0.01 and P < 0.05, respectively).</p><p><b>CONCLUSIONS</b>Serum HBV DNA level of patients with CHB is related to HBV specific CTL, nonspecific CTL and NK cells, which might result in inflammatory reaction of liver and cause more damage to liver function. Mechanism of HBV DNA level affecting the efficacy of anti-viral treatment may be related to the levels of HBV specific CTL and NK cells.</p>