1.Association of chinese medicine constitution and human leukocyte antigen-DQA1 gene polymorphism with outcomes of hepatitis B virus infection.
Yun-hao XUN ; Jun-ping SHI ; Jian-chun GUO
Chinese Journal of Integrated Traditional and Western Medicine 2010;30(2):141-145
OBJECTIVETo observe the Chinese medicine constitution types and human leukocyte antigen (HLA)-DQA1 gene polymorphism in patients with hepatitis B (HB) virus infection in Chinese Han population of Zhejiang Province, for exploring the roles of constitution factor in pathogenesis of HB.
METHODSA total of 240 subjects, including 120 biopsy-proven chronic HB (CHB), 60 HB asymptomatic carrier (ASC) and 60 resolved from HBV infection spontaneously (RHBS) were studied. Their Chinese medicine constitution type was judged by Wangqi's classification, and their genotype of HLA-DQA1 was detected by polymerase chain reaction sequence specific primer for comparing the difference between groups in distribution frequency (DF) of constitution types and genes.
RESULTS(1) As compared with the RHBS group, DF of yin-deficiency constitution and phlegm-dampness constitution in the CHB group was significant higher (20.0% vs. 6.7% and 12.5% vs. 1.7%), and that of placid constitution was significant lower (11.7% vs. 31.7%), showing statistical significance between groups (OR = 3.5, 95% CI: 1.16-10.60; OR = 8.4, 95% CI: 1.09-65.42; OR = 0.161, 95% CI: 0.076-0.34; all P < 0.05). (2) As compared with the ASC group, DF of damp-heat constitution was significant higher (24.2% vs. 6.7%, P < 0.05, OR = 4.462, 95% CI: 1.49-13.36), and that of placid constitution was significant lower (11.7% vs. 45.0%, P < 0.01, OR = 0.285, 95% CI: 0.13-0.62) in the CHB group. (3) As compared with RHBS group, DF of HLA-DQA1 * 0201 allele in CHB group was significant higher (38.3% vs. 5.8%, P < 0.01, OR = 10.04, 95% CI: 4.48-22.48); and that of HLA-DQA1 * 0102 allele was significant lower (9.6% vs. 36.7%, P < 0.01, OR = 0.183, 95% CI: 0.10-0.32). (4) As compared with ASC group, DF of HLA-DQA1 * 0201 allele in CHB group was significant higher (38.3% vs. 7.5%, P < 0.01, OR = 7.667, 95% CI: 3.7-15.87), and that of HLA-DQA1 * 0102 allele was significant lower (20.0% vs. 9.6%, P < 0.01, OR = 0.424, 95% CI: 0.23-0.79).
CONCLUSIONBoth Chinese medicine constitution and HLA-DQA1 gene polymorphism show connection with the outcomes of HB virus infection in Chinese Han population, but the real association between them is required for further study.
Adolescent ; Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Body Constitution ; Carrier State ; virology ; Female ; Gene Frequency ; Genotype ; HLA-DQ alpha-Chains ; genetics ; Hepatitis B ; diagnosis ; genetics ; virology ; Hepatitis B virus ; Heterozygote ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Polymorphism, Genetic ; Young Adult
2.Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNalpha Therapy in HBeAg Positive Chronic Hepatitis B Patients.
Jian-chun GUO ; Xiao-mei DENG ; Jing WU ; Yun-hao XUN ; Xiao-xiao HUANG ; Wei-wei WANG ; Wei-zhen SHI
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(5):539-543
OBJECTIVETo observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy.
METHODSTotally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared.
RESULTSDifferent treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both).
CONCLUSIONSBoth constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.
Antiviral Agents ; therapeutic use ; Gene Frequency ; HLA-DQ alpha-Chains ; genetics ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; genetics ; Humans ; Interferon-alpha ; therapeutic use ; Medicine, Chinese Traditional ; Polyethylene Glycols ; therapeutic use ; Polymorphism, Genetic ; Recombinant Proteins ; therapeutic use ; Remission Induction ; Yin Deficiency ; genetics
3.Study on the correlation between chronic asymptomatic HBV carriers of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles.
Jian-chun GUO ; Li-na XIAO ; Yun-hao XUN
Chinese Journal of Integrated Traditional and Western Medicine 2012;32(8):1038-1041
OBJECTIVETo study on the correlation between chronic asymptomatic HBV carriers (ASC) of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles.
METHODSTotally 105 ASC were assigned to two groups according to their constitutions, i.e., the yin asthenia group (47 cases) and the non-yin asthenia group (58 cases). The genotypes of HLA-DRB1 and HLA DQA1 alleles were determined using PCR-SSP.
RESULTSThe gene frequency of HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele (being 12.1% and 19.1%) were obviously lower in the yin asthenia group than in the non-yin asthenia group (being 27.8% and 39.7%, P < 0.05). The gene frequency of HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele were obviously higher in the yin asthenia group (being 12.1% and 28.7%) than in the non-yin asthenia group (4.3% and 9.5%), showing statistical difference (P < 0.05, P < 0.01).
CONCLUSIONSHLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele might be the molecular bases for non-yin asthenia patients with ASC. HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele might be the molecular bases for yin asthenia patients with ASC.
Adolescent ; Adult ; Carrier State ; Constitution and Bylaws ; Female ; Gene Frequency ; Genotype ; HLA-DQ alpha-Chains ; genetics ; HLA-DRB1 Chains ; genetics ; Hepatitis B, Chronic ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Young Adult
4.Association between HLA-DQA1 gene polymorphism and the outcomes of hepatitis B virus infection
Yun-Hao XUN ; Jian-Chun GUO ; Wei-Zhen SHI ; Jun-Ping SHI ; Chang-Ling LIU
Chinese Journal of Experimental and Clinical Virology 2009;23(6):430-433
Objective To investigate the association between HLA-DQA1 gene polymorphism and the outcomes of hepatitis B virus infection in Chinese Han population.Methods A total of 180 consecutive patients with biopsy-proven hepatitis B virus infection(120 patients with chronic hepatitis B and 60 patients with asymptomatic HBV cartier)and 60 subjects who resolved from HBV infection spontaneously were studied.Genotype of human leukocyte antigen(HLA)-DQA1 was detected by polymerase chain reaction sequence specific primer(PCR-SSP).Results (1)The frequency of HLA-DQA1*0201 allele in chronic hepatitis B group was significant higher than the frequency in resolved from HBV infection spontaneously group(38.3% vs 5.8%,P
5.Clinical research of the relation of hepatitis B surface antigen (HBsAg) quantification and hepatic tissue pathological staging
Xiu-Li YU ; Jian-Chun GUO ; Yun-Hao XUN ; Wei-Zhen SHI ; Yu-Fang WANG ; Wei-Wei WANG ; Wei LIU
Chinese Journal of Experimental and Clinical Virology 2013;27(1):44-46
Objective To explore the correlation of serum hepatitis B surface antigen (HBsAg)level and hepatic tissue pathological staging in the chronic hepatitis B infected persons.Methods Collect the clinical data of 272 cases who are HBsAg-positive more than 6 months and accepted hepatic biopsy in our hospital.Detect serum HBsAg quantification,ALT,HBV DNA,complete blood count,hepatic tissue pathological staging,grouping the cases according to the stage of inflammation and the fibrosis degree respectively.Observe serum HBsAg quantification,HBV DNA and the stage of inflammation and the fibrosis degree.Analyse the correlation between HBsAg quantification and HBV DNA.Results The correlation of serum HBsAg level and HBV DNA is notable.Serum HBsAg level is a variable affecting hepatic tissue pathological stage significantly.Conclusions Serum HBsAg level is a marker having higher specificity and sensitivity to diagnose the hepatic fibrosis.
6.Impact of liver steatosis on antiviral effects of pegylated interferon-alpha in patients with chronic hepatitis B.
Jun-ping SHI ; Lu LU ; Jian-cheng QIAN ; Jian ANG ; Yun-hao XUN ; Jian-chun GUO ; Wei-lin SHI ; Yu-fang WANG ; Jian-gao FAN
Chinese Journal of Hepatology 2012;20(4):285-288
OBJECTIVETo investigate the impact of hepatic steatosis on virologic response in chronic hepatitis B (CHB) patients treated with pegylated interferon-alpha (PEG-IFNa).
METHODSNinety-six naive patients positive for hepatitis B e antigen (HBeAg) and with biopsy-proven CHB were administered PEG-IFNa-2a or PEG-IFNa-2b for 48 weeks. Virologic response (HBeAg clearance and hepatitis B virus (HBV) DNA less than 5 log10 copies/ml) and biochemical response (alanine transaminase (ALT) normalization) were compared between patients with (n=34) and without (n=62) steatosis.
RESULTSThe HBV DNA titer in the steatosis group was significantly lower than that of the non-steatosis group (6.961.27 vs. 7.541.28 log10 copies/ml; t=2.161, P=0.033). After 48 weeks of PEG-IFNa treatments, there was no significant difference in HBeAg seroconversion or the percentage of undetectable HBV DNA (less than 3 log10 copies/ml) between steatosis and non-steatosis patients. However, the steatosis patients presented with a significantly lower complete response rate (virologic response plus biochemical response) compared to non-steatosis patients (26.5% vs. 48.4%; x² =4.373, P=0.037). Of the 45 CHB patients with undetectable HBV DNA after 48 weeks of treatment, seven did not achieve ALT normalization. The rate of patients with non-biochemical response was significantly higher in the steatosis group than in the non-steatosis group (33.3% vs. 6.67%; P=0.032).
CONCLUSIONHepatic steatosis does not affect the virologic response, but does affect the biochemical response in CHB patients treated with PEG-IFNa for 48 weeks.
Adult ; Antiviral Agents ; therapeutic use ; Fatty Liver ; complications ; pathology ; virology ; Female ; Hepatitis B, Chronic ; complications ; drug therapy ; pathology ; Humans ; Interferon-alpha ; therapeutic use ; Liver ; pathology ; Male ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Young Adult
7.Hepatic steatosis: a common reason for elevated alanine aminotransferase levels in HBsAg-positive chronic hepatitis B patients with low HBV DNA loads.
Jun-ping SHI ; Jan-gao FAN ; Gou-qiang LOU ; Li ZHANG ; Chen-bo HU ; Rui WU ; Yun-hao XUN
Chinese Journal of Hepatology 2008;16(11):818-822
OBJECTIVETo evaluate the causes of alanine aminotransferase (ALT) level elevation in HBsAg-positive chronic hepatitis B (CHB) patients with low HBV DNA loads.
METHODSOne hundred nineteen HBsAg positive CHB patients with both serum HBV DNA loads less than 1000 copies/ml and ALT more than 1.25 upper limits of normal (ULN) lasting for at least 6 months were enrolled in this study. Patients co-infected with hepatitis C virus or HIV or suffering from other liver diseases were not included. HBV DNA loads were assayed by PCR. Serological biochemistry and liver biopsy histopathological changes and clinical characteristics of the patients were analyzed.
RESULTSOf the 119 patients 102 were males and 17 were females. The mean age of the patients was (33.9+/-9.7) years and their body mass index (BMI) was (23.4+/-3.7) kg/m2. Mean ALT levels were (150.0+/-166.6) U/L and AST levels were (102.4+/-193.2) U/L. Liver biopsies showed hepatic steatosis in 26.9 % (32/119) of the cases, chronic hepatitis in 53.8% (64/119), non-specific changes in 12.6% (15/119), and 1 without any change. However, hepatic steatosis was more frequently seen in patients taking nucleoside analogs (56.7%), x2=10.394, Probability value less than 0.01. BMI, apolipoprotein B (APO-B), triglyceride, cholesterol and uric acid were all significantly higher in patients with hepatic steatosis than those without (t values were 5.369, 4.276, 3.216, 4.223 and 2.438 respectively, all P less than 0.05) while ALT, AST and apolipoprotein A were much lower in those with steatosis than those without (t values were -2.234, -3.877 and -2.956 respectively, all P less than 0.05). Obesity, dyslipidemia and hyperuricemia were more frequently seen in patients with steatosis than in patients without it (x2 value 3.829, 7.659, 13.389, 0.549, all P less than 0.05). The severity of inflammation and fibrosis were also more significant in patients with steatosis (x2 value 20.978, 17.550, all P less than 0.05). As compared to those patients without specific changes, serum levels of ALT, AST, GGT in patients with chronic hepatitis were obviously higher, all P less than 0.05. In contrast, there were no significant differences in mean age, BMI, male preference, obesity, diabetes, dyslipidemia or hyperuricemia, and the levels of triglyceride, cholesterol, and fasting plasma glucose between the two groups.
CONCLUSIONOur data indicate that hepatic steatosis might be a factor associated with elevated ALT levels in HBsAg-positive CHB patients with low HBV DNA loads, especially in patients treated with nucleoside analogs.
Adult ; Alanine Transaminase ; blood ; Carrier State ; Fatty Liver ; physiopathology ; virology ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; virology ; Hepatocytes ; pathology ; Humans ; Male ; Viral Load ; Young Adult
8.Efficacy and safety of lamivudine plus adefovir combination therapy and entecavir monotherapy for chronic hepatitis B patients.
Jian-Hua YU ; Jun-Ping SHI ; Jing WU ; Xiao-Ou LI ; Jian-Chun GUO ; Yun-Hao XUN ; Chun ZHAO ; Jie JIN ; Ai-Fang XU ; Guo-Qiang LOU
Chinese Journal of Hepatology 2011;19(2):88-92
To compare the efficacy and safety of Lamivudine (LAM) plus Adefovir dipivoxil (ADV) combination therapy and Entecavir (ETV) monotherapy for chronic hepatitis B patients. 120 patients with chronic hepatitis B managed in a single-centre clinical practice (median 96 weeks) were split into 2 cohorts, one was treated with de-novo combination Lamivudine (100 mg/day) plus Adefovir (10 mg/day) (LAM+ADV), the other with Entecavir (0.5 mg/day) monotherapy. Serum levels of ALT, creatinine, HBsAg, HBeAg and HBV viral load, together with genotypic resistence were analyzed at 0, 12, 24, 48, 96 weeks, respectively. HBV DNA was determined by real-time PCR. HBsAg and HBeAg were assessed by chemiluminescence. Serum levels of ALT and creatinine were detected by automatic biochemical analyzer. HBV genotypic resistence was tested by direct sequencing. (1) At the time point of 96 weeks, a total of 99 patients (51 cases in combination therapy cohort and 48 case in monotherapy cohort) were compared. The baseline characteristics as for HBV viral load, median age, serum levels of ALT and creatinine were compatible between combination therapy cohort and monotherapy cohort. (2) The rates of HBV DNA values is less than 300 copies/ml and HBV DNA values is less than 1000 copies/ml had no significant difference between LAM + ADV and ETV cohorts by the 12 and 24 weeks (P more than 0.05). (3) At the time point of 48 weeks, the rates of HBV DNA is less than 1000 copies/ml, HBeAg seroconversion, and ALT normalization were similar in both cohorts, though the rate of HBV DNA values is less than 300 copies/ml was obviously higher in combination therapy cohort than that of monotherapy cohort (90.7% vs 76%, P values is less than 0.05). (4) At the time point of 96 weeks, the rates of HBV DNA values is less than 300 copies/ml (96.1% vs 79.2%), HBV DNA values is less than 1000 copies/ml (98% vs 87.5%) and the HBeAg seroconversion (41.7% vs 16.7%) were markedly higher in combination therapy cohort than those of monotherapy cohort statistically (P values is less than 0.05 for all). The mean values of decreases for HBV viral loads and HBsAg levels were smilar in both cohorts at 48 and 96 weeks. (5) Elevated serum creatinine not be found in both cohorts at the end of treatment. (6) No virological breakthrough occurred in combination therapy cohort at the end of treatment. Four patients in monotherapy cohort were found with virological breakthrough at 96 weeks and three cases among were confirmed to be of variants associated with ETV resistance (rtL180M + T184L + M204V). Present study suggests that Lamivudine plus Adefovir dipivoxil de-novo combination therapy was more efficacious than Entecavir monotherapy for CHB patients and the tolerance is compatible.
9.Clinical and histological features of non-alcoholic fatty liver disease.
Jun-ping SHI ; Yun-hao XUN ; Chen-bo HU ; Li ZHANG ; Hong LIU ; Guo-qiang LOU ; Jian-gao FAN
Chinese Journal of Hepatology 2009;17(11):812-816
OBJECTIVETo investigate the clinical and histological features in Chinese patients with non-alcoholic fatty liver disease (NAFLD).
METHODS108 patients with biopsy-proven NAFLD were enrolled in this study. Clinical, demographic, and biochemical data were compared between NAFLD patients with abnormal ALT and those with normal ALT.
RESULTSSimple fatty liver, nonalcoholic steatohepatitis(NASH) and cirrhosis were diagnosed in 49 (45.4%), 57(52.7%) and 2 (1.9%) patients, respectively. ALT and AST levels of NASH group were higher than those of simple fatty liver group (t = 2.55, 3.13; P = 0.01, 0.00). Fifty of the 77 patients (64.9%) with abnormal ALT levels were diagnosed as non-alcoholic steatohepatitis (NASH), and twenty-six were diagnosed as simple fatty liver, according to liver histology. Among the 31 patients with normal ALT levels, nine (29%) had NASH and twenty-two had simple fatty liver (P = 0.00). The patients with normal ALT had lower necroinflammatory grade than patients with abnormal ALT (x2 = 10.30, P = 0.01), but they had similar degree of steatosis and fibrosis (x2 = 5.52, 6.12; P = 0.12, 0.01). AST, g-glutamyltransferase, total cholesterol, apolipoprotein A1, apolipoprotein B and systolic blood pressure of patients with normal ALT were all lower than those of patients with abnormal ALT (t = 5.91, 2.00, 2.30, 2.10, 3.14, 2.43; P = 0.00, 0.05, 0.02, 0.04, 0.00, 0.02), while spleen thickness and AST/ALT ratio in patients with normal ALT were higher than those with abnormal ALT significantly (t = 3.70, 2.95; P = 0.00, 0.01). Multivariate analysis revealed that ALT (OR = 2.78, 95% CI 1.06-7.3, P = 0.04) was the only independent predictor of NASH, and ALT had low accuracy in predicting NASH, the area under the receiver operating characteristics curves of ALT to predict NASH was 0.69 (95% CI 0.59-0.8, P = 0.00).
CONCLUSIONNAFLD patients have higher ALT level, and elevated serum level of ALT is independent predictor of the degree of inflammation, but not of steatosis and fibrosis.
Adult ; Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Biomarkers ; blood ; Biopsy ; Body Mass Index ; China ; epidemiology ; Fatty Liver ; blood ; epidemiology ; pathology ; Female ; Hepatitis ; blood ; epidemiology ; pathology ; Humans ; Liver ; pathology ; Liver Cirrhosis ; blood ; epidemiology ; pathology ; Male ; Middle Aged ; Prognosis
10.Clinical efficacy of preperitoneal repair with lower abdominal midline incision in inguinal incarcerated hernia
Xiao-Ming JIANG ; Rong-Xun SUN ; Run-Hao CHEN ; Wen-Hai HUANG ; Jian-Ping YU ; Hua-Yun ZHANG
Chinese Journal of Clinical Medicine 2017;24(5):785-788
Objective:To explore the efficacy of preperitioneal tension-free hernia repair by lower abdominal median incision in incarcerated inguinal hernia.Methods:The clinical data of 126 patients with incarcerated hernia who underwent emergency operation from January 2010 to August 2016 were retrospectively analyzed.According to the surgical incision,they were divided into two groups:the observation group (41 cases) had the lower abdominal midline incision,and the control group (85 cases) had the traditional inguinal incision.The time of operation,the postoperative hospital stay,perioperative complications and the main long-term complication were compared between the two groups.Results:In the observation group (41 cases),35 cases underwent preperitoneal tension-free repair (85.4%),1 case recurred and was repaired again,and 2 cases underwent intestinal resection and anastomosis on account of intestinal necrosis.Of the 85 cases in the control group,8 cases recurred and 7 cases underwent reoperation,33 cases underwent first-stage tension-free repair and 1 cases was repaired again,and 3 cases underwent intestinal resection and anastomosis on account of intestinal necrosis.The rate of herniorrhaphy was significantly higher in the observation group than that in the control group (85.4% vs 38.8%,P<0.001).The incidence of total surgical complications (including chronic pain,foreign body sensation,hernia recurrence,incision infection,and local serum swelling) in the observation group was lower than that in the control group (5.7% vs 24.2%,P=0.031).There was no significant differences between the two groups in terms of operation time,hospital stay,perioperative acute pain,and urinary retention.Conclusions:The tension-free repair of preperitoneal hernia through lower abdominal midline incision is simple and can improve the rate of first-stage tension-free repair of incarcerated hernia,and the complication rate is low.It is suitable for clinical application.