Efficacy of pegylated-interferon alpha-2a treatment in patients with HBeAg-positive chronic hepatitis B and partial viral response to nucleoside analogue therapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and related factors of pegylated-interferon alpha-2a (PEG-IFN-2a) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) who achieved partial viral response with nucleoside analogue (NA) therapy.</p><p><b>METHODS</b>Patients with HBeAg-positive CHB and partial viral response to NA treatment were administered a PEG-IFN-2a therapy regimen of 180 g subcutaneous injection once weekly for a personlized duration of time. The existing NA therapy was continued in combination with the new PEG-IFN-2a treatment for 12 weeks. Measurements of serum HBV DNA load, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg and hepatitis B e antibody (anti-HBe) were taken at baseline (prior to addition of the PEG-IFN-2a therapy) and every 3 months afterwards.For determining response to treatment, primary efficacy was defined as undetectable HBsAg and seroconversion, and secondary efficacy was defined as HBsAg less than 10 IU/mL and HBeAg seroconversion.Statistical analysis was carried out using SPSS statistical software.</p><p><b>RESULTS</b>A total of 81 consecutive patients with an average of 12.0 months (range: 6.0-24.0 months) of NA therapy were included in the study and received an average of 19.6 months (range: 15.5-33.3 months) of PEG-IFN-2a treatment. At the end of PEG-IFN-2a therapy, 7 (8.6%) of the patients achieved undetectable HBsAg and seroconversion, and 14 (17.3%) showed HBsAg less than 10IU/mL. In addition, 40.7% achieved undetectable HBeAg and seroconversion, a rate that was slightly higher than that (38.3%) seen in treatment-naive patients who received PEG-IFN-2a. Statistical analyses suggest that baseline level of HBsAg at less than 1500 IU/mL may predict end of PEG-IFN-2a treatment response for HBsAg less than 10 IU/mL, as evidenced by the area under the curve measure of 0.747, sensitivity measure of 87.3%, specificity measure of 33.3%, positive predictive value of 82.1% and negative predictive value of 42.8%.</p><p><b>CONCLUSION</b>Patients with HBeAg-positive CHB and partial viral response to NA therapy can achieve undetectable HBsAg and HBeAg seroconversion after switching to PEG-IFN-2a treatment. Baseline HBsAg level may be predictive of response to this therapeutic strategy.</p>

Study on the etiology of acute hepatitis hospitalized patients in Beijing Ditan Hospital from 2002 to 2011 / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the etiology of acute hepatitis hospitalized patients in Beijing Ditan Hospital from 2002 to 2011.</p><p><b>METHODS</b>We summed up the changes in the characteristics of the etiology of acute hepatitis of patients mentioned above, and preliminarily analyze the causes.</p><p><b>RESULTS</b>From 2002 to 2011, 6235 patients with acute hepatitis were admitted to Ditan Hospital, aged between 12 and 78 years old, Of which 4309 were male and 1926 female. Acute viral hepatitis accounted for 70.44%-85.07%, while CMV, EBV, drug-induced liver injury accounted less than 5%, and acute hepatitis D and acute hepatitis C less than 1.10%. From year to year, the incidence and constitution of acute hepatitis changed significantly. The proportion of patients with acute hepatitis in total hospitalized patients was from 20. 38% to 2.05%. In 10 years, the percentage of acute hepatitis A decreased most obviously, about 99.11%, while 45.07% decline in incidence of acute hepatitis B and 62. 28% of acute hepatitis E. The constituent ratio of acute hepatitis also changed significantly. The proportion of acute hepatitis A declined from 31.31% in 2002, to less than 1% in 2011. The proportion of acute hepatitis B increased from 26.47% in 2002 to 45.88% in 2011, an increase of about 2 folds in 10 years. The proportion of acute hepatitis E increased from 26.73% in 2002 to 32.05% in 2010, a rise of 1.20 times in 10 years.</p><p><b>CONCLUSIONS</b>The proportion of patients with acute hepatitis in total hospitalized patients decreased from 20. 38% in 2002 to 2. 05% in 2011 in Beijing Ditan Hospital. The constituent ratio of acute hepatitis changed, too.</p>

Analyse related factors of impact and prognosis of 73 cases of severe hepatitis / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>A retrospective study was conducted to investigate the clinical features and prognostic factors of 73 cases of severe hepatitis.</p><p><b>METHODS</b>To summarize clinical features of 73 cases of severe hepatitis, grouping by etiology and pathogenesis. A retrospective analysis was performed to evaluate the relationship between biochemical characteristics (liver function, renal function, electrolytes, PTA, etc) and complications (hepatic encephalopathy, upper gastrointestinal bleeding, hepatorenal syndrome, ascites, abdominal infections, etc) and prognosis.</p><p><b>RESULTS</b>(1) HBV infection alone accounted for 65.75%. Alcoholic liver disease, drug-induced liver injury, hepatitis E, autoimmune hepatitis, overlapping causes and other factors were five cases (6.85%), six cases (8.22%), two cases (2.74%), two cases (2.74%), seven cases (9.59%) and three cases (4.11%) respectively. According to the incidence rate, severity and underlying liver condition, subacute hepatitis, cases based on chronic hepatitis and on cirrhosis were 12 cases (16.43%), 11 cases (15.07%), 50 cases (68.49%) respectively. Clinical manifestations with or without hepatic encephalopathy accounted for 58.90% or 41.10%. (2) The highest mortality of severe hepatitis was alcoholic liver disease and patients on the basis of overlapping factors (66.67%), followed by autoimmune liver disease (50%). The mortality of HBV-related hepatitis was 18.75%. Overall mortality of 73 cases of severe hepatitis was 28.77%, of which cirrhosis group was higher than non-cirrhotic group (40% vs 4.3%, P = 0.002). The difference was statistically significant. Patients without hepatic encephalopathy had lower mortality than with hepatic encephalopathy (3.33% vs 46.51%). The mortality of patients with hepatic encephalopathy Stage III and IV was 72.73%. (3) Independent samples t test filtered nine factors associated with death, namely cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, serum creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB) and serum sodium. The results of multivariate conditional logistic regression analysis indicated that hepatic encephalopathy, serum creatinine levels were risk factors for death, whereas ALB as a protective factor.</p><p><b>CONCLUSION</b>Hepatic encephalopathy, serum creatinine levels were risk factors for severe hepatitis death, But ALB was protective factor. Nucleotide analogs using was the main reason why the mortality of hepatitis B was as low as 18.75%.</p>

Clinical study on viral hepatitis combined with aplastic anemia / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the clinical features, outcomes and treatments of viral hepatitis combined with aplastic anemia.</p><p><b>METHODS</b>25 cases diagnosed as viral hepatits combined with aplastic anemia in Beijing Ditan Hsopital between April 2004 and September 2009 were retrospectively analyzed. In this group of patients aplastic anemia was finally diagnosed by bone marrow aspiration. We collected clinical data of these patients, including a history of liver disease, drug allergies, hospital medication history, laboratory data, and then performed descriptive analysis.</p><p><b>RESULTS</b>25 patients with viral hepatitis were diagnosed as complicated with aplastic anemia by histopathological data. Among these patients, 17 were male and 8 were women. Viral hepatitis included: chronic hepatitis B (12 cases), chronic hepatitis C (4 cases), acute hepatits E (1 case), hepatitis caused by CMV infection (1 case), and unclassified hepatitis (7 cases). Among these patients, 7 were diagnosed as severe hepatits. Considering previous history, only 3 patients had history of short term interferon therapy before hospitalization, and the remaining patients did not use drug that affects blood system. Treatments were as followings: using colony stimulating factor in 6 patients, gamma globulin in 9 patients, glucocorticoids in 3 patients, erythropoietin in 1 patient, only oral drug to raise erythrocytes in 2 patients, red blood cells transfusion in 6 patients, platelets transfusion in 2 patients. As for clinical outcomes, 20 patients acquired improved condition and were dicharged, 3 patients were discharged voluntarily and 2 patients died of severe hepatits combined with other complications.</p><p><b>CONCLUSION</b>Main treatments of viral hepatitis combined with aplastic anemia were to treat primary hepatopathy and nucleoside analogue-based antiviral therapy, to provide symptomatic and supportive treatment for blood diseases. Blood diseases would recover simultaneously while liver disease was improved, and the prognosis was good.</p>

Factors associated with HBeAg seroconversion in chronic hepatitis B patients treated with interferon alfa-2a / 中华肝脏病杂志

<p><b>OBJECTIVE</b>The aim of this paper was to investigate the factors associated with viral response and HBeAg seroconversion and the relationship between them at different stages of interferon treatment in HBeAg-positive chronic hepatitis B patients.</p><p><b>METHODS</b>PEG-IFN alfa-2a was injected subcutaneously in doses of 180 microg once a week for 48 weeks to HBeAg-positive chronic hepatitis B patients, and the patients were followed for another 24 weeks after the treatment. The serum HBV DNA load was measured by real-time quantitative PCR assay. Microparticle enzyme immunoassay analysis (MEIA) was then carried out by an automatic enzyme immunoassay analysis instrument to measure HBeAg and anti-HBe. Virological response and HBeAg seroconversion rates, and the factors associated with them were analyzed.</p><p><b>RESULTS</b>The differences in ALT baselines between viral responding and non-responding groups were significant at treatment time and at the end of the follow-up period. These differences were also significant in patients with HBeAg seroconversion at 12 weeks and at the end of the follow-up period compared with the non-conversion group. No significant difference of HBV DNA baseline was observed between the HBeAg seroconversion and non-conversion group. At 12, 24 and 48 weeks, in patients with viral response during the treatment, their HBeAg seroconversion rates were 43.8%, 21.4% and 18.9% respectively; their respective HBeAg seroconversion rates remaining at 72 weeks were 42.9%, 33.3% and 27.6%. HBeAg seroconversion was related to HBV DNA negativity at 48 weeks treatment in the multivariate analysis (OR=2.15, 95.0% CI=1.744-2.664, P less than 0.01).</p><p><b>CONCLUSIONS</b>Viral response and early and sustained HBeAg seroconversion were associated with pretreatment ALT levels. HBeAg seroconversion was related to viral response during IFN treatment, but not to the baseline HBV DNA load.</p>

Factors related to the outcome of patients with chronic severe hepatitis B and effectiveness of antivirus therapy / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the factors related to the outcome of patients with chronic severe hepatitis B and effectiveness of antivirus therapy.</p><p><b>METHODS</b>The effects of the factors including age, prothrombin activity (PTA), serum HBeAg, Anti-HBe, HBV-DNA load, with or without complication, antivirus therapy and so on, on outcome of 330 patients with chronic severe hepatitis B were analyzed in this retrospective study.</p><p><b>RESULTS</b>The mortality of patients with chronic severe hepatitis B was significantly higher among patients at higher age, with lower PTA, and with more complications. The mortality of patients with HBV-DNA more than 1x10(5) copies/ml (52.3 percent) was higher than that of patients whose HBV-DNA was less than 1x10(5) copies/ml (32.9 percent). There was no correlation between serum HBeAg or anti-HBe and the mortality. The mortality of patients with HBV-DNA higher than 1x10(5) copies/ml (30.38 percent) who were treated with lamivudine in 2005 was lower than that of patients whose HBV-DNA was less than 1x10(5) copies/ml (54.64 percent) who were not treated with any antiviral therapy in 2001.</p><p><b>CONCLUSION</b>The higher serum virus load is the key factors of the mortality in addition to the other factors such as older age, lower PTA, more complication in the patients with chronic severe hepatitis B. The usage of antivirus therapy may be associated with lower mortality.</p>

Association of polymorphisms of human leucocyte antigen -DRB1 and -DQA1 allele with outcomes of hepatitis B virus infection in Han population of north China / 中国医学科学院学报

<p><b>OBJECTIVE</b>To assess the association of polymorphisms of human leucocyte antigen (HLA) -DRB1 and -DQA1 region allele with outcomes of hepatitis B virus (HBV) infection in Han population of north China.</p><p><b>METHODS</b>A total of 207 chronic hepatitis B (HB) patients, 212 chronic asymptomatic HBV carriers (HBV carrier), and 148 self-limited HBV infection were recruited to examine the association between gene polymorphisms and outcomes of HBV infection. Polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to genotype HLA-DRB1 and HLA-DQA1 loci.</p><p><b>RESULTS</b>The frequency of HLA-DQA1 * 0301 in chronic HB patients (14.81%) was significantly lower than those in HBV carriers (25.24%) and self-limited HBV infection subjects (25.00%) (Pc = 0.002; Pc = 0.007). The frequency of HLA-DQA1 * 0102 in self-limited HBV infection subjects (8.78%) was significantly higher than those in chronic HB patients (2.18%) and HBV carriers (1.89%) (Pc = 0.000; P = 0.000). In addition, the frequency of HLA-DQA1 * 0302 in self-limited HBV infection subjects (4.05%) was significantly lower than that in chronic HB patients (11.41%) (Pc = 0.005). HLA-DQA1 * 0302 was demonstrated to be risk factors of chronic HBV (OR = 3.913, P = 0.0006), while HLA-DQA1* 0102 and HLA-DQA1 * 0301 to be protective factors against chronic HBV (OR = 0.200, P = 0.0004; OR = 0.258, P = 0.0000) after age, sex, smoking and drinking were adjusted by logistic regression analysis. There were positive interactions between drinking and HLA-DQA1 * 0102 [interaction index (II) = 1.49] or HLA-DQA1 * 0302 (II = 12.12). There were negative interactions between drinking and HLA-DQA1 * 0301 (II = 0.78)</p><p><b>CONCLUSIONS</b>The subjects with HLA-DQA1 * 0302 allele have an increased risk to chronic HB infection compared with other subjects without this allele, while HLA-DQA1 * 0301 and HLA-DQA1 * 0102 are associated with HBV clearness. Gene-environment interaction can affect the outcomes of HBV infection.</p>

An analysis of the relationship between HBV DNA and HBeAg expression and mortality in 799 severe hepatitis patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between mortality and HBVDNA and HBeAg expression of severe hepatitis B patients.</p><p><b>METHODS</b>The mortality rates of different types of severe hepatitis patients in our hospital during the last five years were analysed. HBV DNA was detected using the fluorescence quantitative PCR method and the HBeAg expression of severe hepatitis B was studied using a microparticle method.</p><p><b>RESULTS</b>(1) Hepatitis B morbidity was 83.5% in each type of severe hepatitis, and severe chronic hepatitis B morbidity was 96.77% in each type of severe chronic hepatitis. (2) The mortality rate of those with HBV DNA more than 1 x 10(5) copies/ml was 53.25% and the mortality of those with HBV DNA less than 1 x 10(5) copies/ml was 34.50% (P less than 0.01). The HBeAg expression had no influence on the death rate. (3) The death rate descended to 30.38% from 54.64% (HBV DNA more than 1 x 10(5) copies/ml) when treated with Lamivudine (P less than 0.01).</p><p><b>CONCLUSION</b>In severe hepatitis the quantity of virus carried in the patient is one of the key factors of mortality; antivirus treatment can lower mortality.</p>