Relation between serum levels of high mobility group box 1 and hepatitis B virus-related acute-on-chronic liver failure / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the levels of high mobility group box 1 protein (HMGB1) in serum of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) and investigate its potential relation to the clinical features of these patients.</p><p><b>METHODS</b>Sixty patients with HBV-related ACLF, 30 patients with chronic hepatitis B (CHB), and 24 healthy individuals (controls) were enrolled in the study. Markers of liver function, such as aspartate aminotransferase (AST), were measured by routine biochemical methods. Imaging studies, such as abdominal computed tomography or magnetic resonance imaging, were used for disease staging. Serum levels of HMGB1 were measured by ELISA. Deaths within the 2-month follow-up after serum collection were used for the survival analysis. Patients who developed peritonitis, pneumonia, or other bacterial and fungal infections during the 2-month follow-up after serum collection were classified as the infected group. Pairwise comparisons were carried out by t-test, and multiple comparisons were carried out by analysis of variance.</p><p><b>RESULTS</b>Patients with HBV-related ACLF had significantly higher serum levels of HMGB1 than CHB patients or controls (P = 0.003). Among the patients with HBV-related ACLF, those in the late stage (n = 20) had significantly higher levels of HMGB1 than those in the early stage (n = 20) (P = 0.005). The serum levels of HMGB1 correlated well with AST level in patients with HBV-related ACLF (P = 0.006). In addition, patients with HBV-related ACLF who developed infection or died during follow-up also had significantly higher levels of HMGB1 (P = 0.028 or P = 0.017, respectively).</p><p><b>CONCLUSION</b>Enhanced serum level of HMGB1 is associated with development of HBV-related ACLF in CHB patients. The strong correlation between HMGB1 and AST levels suggest that HMGB1 may be useful as a prognostic marker for development of ACLF.</p>

Orthogonal design based optimization of a mouse model of acute liver failure induced by D-galactosamine and lipopolysaccharide / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To apply an orthogonal design optimization strategy to a mouse model of acute liver failure induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) exposure.</p><p><b>METHODS</b>A four-level orthogonal array design (L16(45)) was constructed to test factors with potential impact on successful establishment of the model (D-GalN and LPS dosages, and dilution rate of the D-GalN/LPS mixture). The mortality rate of mice within 24 hours of D-GalN/LPS administration was determined by the Kaplan-Meier method. The model outcome was verified by changes in serum alanine transferase level, liver histology, and hepatocyte apoptosis.</p><p><b>RESULTS</b>The orthogonal array identified the optimal model technique as intraperitoneal injection of a combination of D-GalN and LPS at dosages of 350 mg/kg and 30 mug/kg, respectively, and using a dilution rate of 3. The dosages tested had no effect on survival. The typical signs of liver failure appeared at 6 hrs after administration of the D-GalN/LPS combination.</p><p><b>CONCLUSION</b>The orthogonal design optimization strategy provided a procedure for establishing a mouse model of acute liver failure induced by D-GalN and LPS that showed appropriate disease outcome and survival, and which will serve to improve future experimental research of acute liver failure.</p>

Clinical analysis of 134 cases of HEV-related liver failure / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the clinical features of hepatitis E virus-related liver failure.</p><p><b>METHODS</b>134 patients with HEV-related liver failure were analyzed retrospectively.</p><p><b>RESULTS</b>HEV-related liver failure accounted for 8.45 percent of the total number of hepatitis E patients in the hospital. Of the 134 patients, 68 were infected with simple HEV, 66 had the superinfection with HBV. The average age of simple HEV-related liver failure patients (56.12 +/- 14.29) was higher than that of HBV superinfectiong liver failure patients (P < 0.05). The ratio of elderly patients (> or = 60 years) in simple HEV-related liver failure patients (45.59%) was significantly higher than that of the other group (13.64%, P < 0.05). The ratio of direct bilirubin/total bilirubing (0.72 +/- 0.07, 0.69 +/- 0.08), and serum alanine aminotransferase [(1250.90 +/- 1593.97) U/L, (616.26 +/- 797.62) U/L] were significantly higher in simple HEV-related liver failure patients than in HBV superinfectiong liver failure patients (P < 0.05), but the total bilirubing had no significant difference (P > 0.05). The disease outcome and stage were no-significant difference in the two groups (P > 0.05). CONCLUSION; Simple HEV-related liver failure patients may have older age, higher aminotransferase, higher ratio of direct bilirubin/total bilirubin, but disease outcome and stage were no-significant difference in the two groups.</p>

Clinical and pathological analysis of 566 patients with cryptogenic liver diseases / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the etiology, pathology, and clinical characteristics of cryptogenic liver diseases in order to develop a pathogenic profile for clinical diagnosis and therapeutic design.</p><p><b>METHODS</b>The data of the 566 patients diagnosed with abnormal liver function and who had undergone liver biopsy at our institute between January 2006 to March 2010 were retrospectively analyzed. The Chi-squared (x²) test was used to assess disease correlation with sex and the rank sum test was used to assess disease correlation with continuous data since all data had asymmetric distribution.</p><p><b>RESULTS</b>Among the 566 patients, abnormal liver function was attributed to alcoholic liver disease (n=175; 30.92%), drug-induced or environmentally-induced liver disease (n=101; 17.84%), hereditary and metabolic disease (n=93; 16.43%), infectious hepatitis disease (n=84; 14.84%), fatty liver disease (n=53; 9.36%), and autoimmune liver disease (n=30; 53.00%). Thirty patients had unknown etiology, despite liver biopsy analysis. Among these disease subgroups, there were distinct correlations with sex, age, and levels of alanine transaminase (ALT) and gamma-glutamyltransferase (GGT). The autoimmune liver disease group was correlated with sex (q=9.14, 7.435, 5.071, 9.529, and 12.5, respectively; P less than or equal to 0.01). The alcoholic liver disease group and autoimmune liver disease group were correlated with age (vs. genetic metabolic disease group: q=17.254 and 10.302; infectious hepatitis group: q=17.523 and 10.697); drug/environmentally-induced liver damage group: q=9.170 and 5.266); fatty liver group: q=7.118 and 4.661) (P less than or equal to 0.01). In addition, the alcoholic and autoimmune liver disease groups were correlated with GGT levels (vs. genetic metabolic disease group: q=8.003; infectious hepatitis group: q=4.793; drug/environmentally-induced liver damage group: q=4.404) (P less than or equal to 0.01).</p><p><b>CONCLUSION</b>Liver pathology is important for the diagnosis of cryptogenic liver diseases. Patient age, sex, and biochemistry index may facilitate diagnosis and treatment in the absence of pathology.</p>

Clinical study on hybrid bioartificial liver supporting system for acute on chronic liver failure patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To construct an hybrid bioartificial liver supporting system, and observe its effectiveness and safety on patients with acute on chronic liver failure.</p><p><b>METHODS</b>Hybrid bioartificial liver supporting system (HBALSS) was constructed using bioreactor with HepG2 cells transfected with human augmenter of liver regeneration (hALR) gene. 12 acute on chronic liver failure patients were divided into 2 groups randomly. The treatment group was treated with the hybrid bioartificial liver support system. The group underwent plasma exchange was used as control.</p><p><b>RESULTS</b>In the treatment group, four patients recovered, one patient died of hepatic encephalopathy, one patient died of hepatorenal syndrome, one patient recovered, but died of gastrointestnal bleeding after 1 year. In control group, two patients recovered, one patient underwent orthotropic liver transplantation, and three patients died of liver failure.</p><p><b>CONCLUSION</b>The hybrid bioartificial liver supporting system with HepG2 cell line was established successfully and have certain safety and effectiveness on acute on chronic liver failure patients.</p>

Clinical characteristics of hepatitis B virus-related acute-on-chronic liver failure patients with familial aggregation / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of hepatitis B virus-related acute-on-chronic liver failure patients with familial aggregation.</p><p><b>METHODS</b>275 patients with hepatitis B virus--related acute-on-chronic liver failure were investigated. The patients were divided into familial aggregation and non-familial aggregation group basis on their epidemiological features. Clinical data and biochemical indicators between the two groups were analyzed statistically.</p><p><b>RESULTS</b>93 of 275 patients (33.82%) case were family aggregation. There was no significant difference compared with chronic hepatitis B patients (38.3%). The mean age of the two groups was 45.98 and 43.61 years old, respectively (P > 0.05). The rates of liver cirrhosis in family aggregation group were significant higher than non-familial aggregation group (73.91% vs 58.24%, p < 0.05). Serum total (TBil) and prothrombin activities (PTA) were no significant difference between the two groups, but ALT level in familial aggregation group was much higher (407.80 U/L vs 256.45 U/L, P 0.05).</p><p><b>CONCLUSION</b>Familial aggregation were not related to acute-on-chronic liver failure in chronic HBV hepatitis patients. But the rate of liver cirrhosis were higher in patients with familial aggregation.</p>

Distribution and clinical significance of HBV genotypes in patients with HBV infection in 30 regions of China / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the distribution and clinical significance of HBV genotypes in patients with HBV infection in China.</p><p><b>METHOD</b>Serum samples were collected from 2922 patients with HBV infection. HBV genotyping was performed with type-specific primers polymerase chain reaction, and the virological and biochemical markers were detected, which differences in the genotypes distribution between various regions and liver function and virological markers between various HBV genotyping were analyzed.</p><p><b>RESULT</b>The genotype B, C, B + C, D of 2922 patients with HBV infection accounted for 15.9%, 83.5%, 0.41%, 0.21% respectively. In Northern China, genotype C was most prevalent, accounting for 90% of all cases, while it was less common in Southern China; genotype C was present in Zhejiang and Jiangsu provinces, but genotype B was comparatively more common in Guangdong, Hunan, Hubei, and Jiangxi provinces. B, C genotype HBV infection patients in the sex difference was not statistically significant; B genotypes compared with C genotype HBV infection patients, the average age of is less (P < 0.001); HBeAg positive rate of C genotype HBV infection patients are higher than that of B genotype (P = 0.023); Viral load of genotype C HBV infection patients is higher than that of genotype B (P = 0.038); Cholinesterase and Albumin levels of genotype C HBV infection patients are lower than that of genotype B (P values were 0.016, <0.001).</p><p><b>CONCLUSION</b>There were HBV genotype B, C, B + C and D in Chinese patients with HBV infection, with genotype B and C being the major ones. Mainly in northern regions of genotype C, C genotype significantly reduced the southern region, some of the southern region dominated by B genotype. Genotype C HBV infection patients are older, and their HBeAg-positive rate is higher, and their liver damage is more severe, but their viral load is less.</p>

Characterization of hepatitis B virus genotypes/subgenotypes in 1,301 patients with chronic hepatitis B in North China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There is still a paucity of data on hepatitis B virus (HBV) subgenotype prevalence in North China based on sequencing of large-size samples. In addition, whether HBV genotypes impact drug-resistance-associated and HBV e antigen (HBeAg)-loss-associated mutations in patients with chronic hepatitis B (CHB) is still under investigation. This study aimed to disclose clinical prevalence of HBV genotypes/subgenotypes in North China and the clinical implications of HBV genotype classification in respect to HBeAg loss and drug-resistant occurrence.</p><p><b>METHODS</b>Sera were collected from 1301 nucleos(t)ide analog-experienced CHB patients. Viral DNA was extracted and used as template for HBV genome amplification by nested PCR. DNA sequencing was performed for the analysis of HBV genotypes/subgenotypes, drug-resistance-associated mutations in polymerase gene and HBeAg-loss-associated mutations in precore/basal core promoter (BCP) regions.</p><p><b>RESULTS</b>HBV/B, HBV/C, and HBV/D were detected in 190 (14.6%), 1096 (84.2%), and 15 (1.2%) patients, respectively. HBV/B2 (182/190), HBV/C2 (1069/1096), and HBV/D1 (12/15) were predominant subgenotypes within individual genotypes. By contrast, C2 prevalence is relatively lower in Beijing area (77.2%) than in other north areas (84.9% - 87.4%). HBV/C-infected patients had an older age and a lower serum albumin level but similar HBV DNA and alanine aminotransferase (ALT) levels compared to HBV/B-infected patients. HBV/C infection had a higher incidence of lamivudine-resistant mutations rtM204I/V (44.9% vs. 30.2%, P < 0.01) and BCP mutations A1762T+G1764A (65.8% vs. 40.0%, P < 0.01) compared with HBV/B infection.</p><p><b>CONCLUSIONS</b>C2 is the most prevalent HBV subgenotype followed by B2 in CHB patients in North China; and HBV genotype prevalence is influenced by immigrant population. HBV/C infection is likely to have longer disease duration and severer liver functional impairment and might be more susceptible to develop lamivudine resistance compared to HBV/B infection.</p>

Construction and experimental study on off-line hybrid bioartificial liver supporting system with human liver cell line / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To construct an off-line hybrid bioartificial liver supporting system with human liver cell line, and study it's effect on the plasma from patients with liver failure.</p><p><b>METHODS</b>We established the bioreactor using Psu-2s (Fresenius) cultured with Hep G2 cell transfected with human augmenter of liver regeneration (hALR) gene, then constructed a hybrid bioartificial liver supporting system, at last using the bioartificial liver support system to purify the plasma treated 2 hours with serum bilirubin absorbent, separated from acute on chronic liver failure patients infected by hepatitis B virus.</p><p><b>RESULTS</b>Bioreactor was successful constructed. The cell viability in perigastrum of bioreactor is 85.2% and cell propagated rapidly. Before and after treating with bilirubin absorbent, serum total bilirubin was (176.19 +/- 54.14) micromol/L and (50.1 +/- 16.85) micromol/L respectively (P = 0.0002). While there were no significance difference in the level of albumin, urea and glucose. At the begin and end of treatment with bioartificial liver, serum total bilirubin was (50.10 +/- 16.85) micromol/L and (30.27 +/- 15.02) micromol/L respectively (P = 0.000), the urea and albumin increased, urea has significantly difference, but the change of albumin hasn't.</p><p><b>CONCLUSION</b>The off-line hybrid bioartificial liver supporting system with human liver cell line were builded successfully and have synthesis and metabolism functions for acute on chronic liver failure patients.</p>

Estimation of liver inflammation and necrosis in patients with chronic hepatitis B through different biochemical items / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To establish a new grading system to evaluate liver inflammation and necrosis in patients with chronic hepatitis B through clinical biochemical assays.</p><p><b>METHODS</b>Clinical and pathological data were collected from 255 cases with chronic hepatitis B. 19 biochemical items were analyzed and 5 items were selected for our grading system. Each of the five items was scored 0 to 4 based on the different values. The extent of liver inflammation and necrosis was evaluated according to the total score.</p><p><b>RESULTS</b>ALT, AST, ChE, GGT and TBA were selected for our grading system. The grade of liver inflammation and necrosis was considered less than 2.0 if total score lower than 6, and higher grade was considered with higher total score. The estimated results shared an identity of 82.8% with the real grades of liver inflammation and necrosis. When this grading system was applied to patients with liver inflammation and necrosis equal to or higher than grade 2.0, it exhibited a sensitivity of 83.8%, a specificity of 81.2%, a positive prediction value of 88.6%, a negative prediction value of 74.2% in all cases, and 88.0%, 84.7%, 90.6%, 82.4% respectively in patients older than 12 years.</p><p><b>CONCLUSION</b>Our data suggest that the grading system can be used to evaluate the extent of liver inflammation and necrosis in patients with chronic hepatitis B.</p>

Primry research of separation and culture of adult hepatocytes / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the separation and culture method of adult hepatocytes.</p><p><b>METHODS</b>The isolated adult hepatocytes were cultivated by RPMI 1640 medium at 37 degrees C in vitro. The characteristics of the growing hepatocytes were observed. Their synthesis of urea was detected. The transformation efficiency and density's change of lidocaine were analyzed.</p><p><b>RESULTS</b>Hepatocytes were successful separated from adult liver. And they were cultivated in common condition and hollow fiber reactor. The functional capacity of hepatocytes was for lidocaine metabolism and urea excretion.</p><p><b>CONCLUSION</b>The adult hepatocytes have been successful separated from liver. And they can be cultivated in common condition and hollow fiber reactor. And it could provide a great quantity and high activity of hepatocytes for bioartificial liver.</p>

Immune effects of mutated hepatitis B virus precore-core DNA vaccines in mice / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To observe the immune effect of DNA vaccines encoding mutated HBV pre-c/c gene (VE2,VE4) in mice.</p><p><b>METHODS</b>Three kinds of plasmid VEC(DNA vaccines encoding HBV pre-c/c gene), VE2 and VE4 were injected into the thigh muscles of different group of BALB/c mice.Blood and splenocytes from mice were isolated at 4 weeks after immunization. We also have mouse groups immunized with three of these plasmid combined with IFN-gamma gene plasmids. The anti-HBc and anti-HBe antibody in peripheral blood in mice were detected by enzyme linked immunosorbent assay (ELISA), antigen-specific cell immune responses were detected by CTL test and enzyme linked immunospot assay(ELISpot).</p><p><b>RESULTS</b>We found that anti-HBe titers of VE2 and VE4 immunizing groups are higher than VEC group (P < 0.05). We also observed that VE2 and VE4 could induce stronger antigen-specific immune responses than VEC and when combined with IFN-gamma plasmid,the antigen-specific immune responses are stronger than those without combination immunization in mice (P < 0.05).</p><p><b>CONCLUSIONS</b>The DNA vaccine VE2 and VE4 could induces stronger antigen-specific immune responses than VEC, and when combined with IFN-gamma plasmid,the antigen-specific immune responses are improved in mice.</p>

Primary application of identification-aided system for diagnosis and differential diagnosis of emerging infectious diseases / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To verify the rate of diagnostic fitting between the clinic and the indentification-aided for diagnosis and differential diagnosis system, for emerging infections diseases (EID) established.</p><p><b>METHODS</b>314 cases of 49 kinds of contagious diseases diagnosed and another 186 patients with fever who not diagnosed were tested by the system.</p><p><b>RESULTS</b>Preliminary verification was made in 314 cases diagnosed which classified to 49 kinds of contagious diseases of infectious diseases and the results showed that the coincidence rate of clinical diagnosis and first diagnosis of this system was 61.9%; the suggestive rate of first three diagnoses was 78.1%, and that of first five diagnoses was 86.6%. The diagnosis of another 186 patients with fever were diagnosed by the system and the results showed that the coincidence rate of clinical diagnosis and first diagnosis was 59.7%; the suggestive rate of first three diagnoses was 77.9%, and that of first five diagnoses was 85.4%.</p><p><b>CONCLUSIONS</b>The system can accurately suggest impossible diagnosis and differential diagnosis, and be useful for our medical work.</p>

Construction and antigenic evaluation of a recombinant MVA virus-like particle expressing HBV C gene / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct the virus-like parcel expressing hepatitis B virus (HBV) C gene and identify its immunogenicity.</p><p><b>METHODS</b>HBV C gene was cloned into the shuttle vector pSC11, and the resulted plasmid pSC11-C was transfected into modified vaccinia virus Ankara (MVA).</p><p><b>RESULTS</b>pSC11-C was correctly constructed as verified by sequence analysis and PCR, and the recombinant virus-like parcel possessed good immunogenicity.</p><p><b>CONCLUSION</b>The MVA-C expressing HBV C gene has been successfully constructed to provide important basis for gene therapy research of chronic HBV infection.</p>

Liver pathological changes and clinical features of patients with chronic hepatitis B virus infection in their immune tolerant phase and non-active status / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the liver pathological changes and the clinical features of patients with hepatitis B virus (HBV) infection in their immune tolerant phase and non-active status.</p><p><b>METHODS</b>Fifty-four patients with chronic HBV infection in their immune tolerant stage and another 47 patients with the same infection but in non-active status were involved in this study. Statistical analysis including the ages and sex of the patients, their serum levels of HBV DNA, hepatocytic expression of HBsAg and HBcAg and their liver pathology were studied and statistically analyzed. Histological grading of inflammation and staging of fibrosis in the livers were also compared and analysed in patients with different levels of serum ALT.</p><p><b>RESULTS</b>The sex ratio of the two groups was of no significant difference. The average age of the patients in the non-active status [(28.11+/-8.60) years.] was older than that of the patients in the immune tolerant stage [(24.93+/-7.21) years], showing a significant difference (P < 0.05). The serum levels of HBV DNA of the patients in the immune tolerant stage were high and 94% of them had a HBV DNA higher than 106 copies/ml. In the non-active status group, 89% of the patients were HBV DNA negative. Between the two groups of patients there were no significant differences in the histological grades of liver inflammation or in the hepatocytic expressions of HBsAg and HBcAg. The stage of fibrosis was higher in the non-active status group than in the immune tolerant stage group, showing a significant difference between these two groups (u = 2.004, P < 0.05). The fibrosis stages of the livers of patients of a higher but within normal ALT level were markedly higher than those of a lower but within normal ALT level patients (u = 3.274, P less than 0.01).</p><p><b>CONCLUSION</b>Patients infected with HBV in non-active status may have experienced some occult courses of immune active stages; they are older in age and have higher levels of fibrosis. ALT sustained at a high level but within the normal range may indicate a higher degree of fibrosis, therefore liver pathological studies should be recommended for this kind of patient.</p>

Research of hepatic pathology and clinical characteristics of patients chronic infected with hepatitis B virus in immune tolerant stage / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the characteristics of the hepatic pathological and clinical features of patients with hepatitis B virus (HBV) in immune tolerant stage and find the better measure of diagnosing patients chronic infected by HBV in immune tolerant phase.</p><p><b>METHODS</b>135 patients with HBV chronic infection and persistently normal serum alanine aminotransferase (ALT) levels were involved in this study, whose serum HBeAg and HBV DNA were positive. Statistical analysis included the ages, sex, serum levels of HBVDNA, ALT and histological grade. The grades of inflammation and fibrosis were obtained through hepatic biopsy performed on all the patients.</p><p><b>RESULTS</b>Mean age in those patients was 22.61 +/- 8.95 years old. All those patients were divided into two groups according to histological grade: low- histological grade group, G < or = 1 and S < or = 1; and high-histological grade group, G > or = 2, S > or = to 2. Levels of histological grade were low in most of patients (99/135). Patients of low-histological grade had no difference in age, sex and family history of HBsAg carriers. Compared with low-normal ALT (ALT less than 30U/L), those with high-normal ALT (ALT > or = 30U/L) had a greater frequencies of high-histological grade. Compared with high HBVDNA (HBVDNA > or = 10(7) copies/ml), those with low HBVDNA (HBVDNA less than 10(7) copies/ml) had a greater frequencies of high-histological grade.</p><p><b>CONCLUSION</b>Levels of histological grade were low in most of patients with HBV chronic infection, serum HBeAg and HBVDNA positive, persistently normal serum ALT levels, but some of them were high-histological grade. It showed those patients were not all in immune tolerant stage of chronic HBV infection. Examination of ALT and HBVDNA are helpful to evaluate hepatic pathological damage for them.</p>

Survival analysis on liver failure patients treated with an artificial liver support system / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of artificial liver support system (ALSS) in the treatment of liver failure patients.</p><p><b>METHODS</b>This is a prospective, multi-center, controlled, large sample clinic trial. 518 patients with liver failure from 5 hospitals were studied and followed. All the patients received similar pharmacological manipulation according to one and the same protocol but were divided into an ALSS treatment group and a control group without ALSS treatment. The ALSS treatment procedures included plasma exchange, molecular adsorbent recirculating system (MARS), plasma exchange plus hemofiltration and other combined nonbioartificial methods. The analysis of survival time was computed using the Kaplain-Maier method, and comparison among groups was done using Log-Rank, Breslow and/or the Tarone-Ware test.</p><p><b>RESULTS</b>Survival time of acute liver failure patients was prolonged from 4.0+/-0.2 days to 8.0+/-0.4 days (P=0.004). ALSS was shown to be two times more effective. ALSS increased the survival time of acute on chronic (A on C) liver failure patients from 27.0+/-1.6 days to 39.0+/-4.0 days (P less than 0.01). In addition, it increased the survival time of the patients in the middle and end stage of subacute liver failure and A on C liver failure, but had no significant effects on early stage patients. The survival time of middle stage patients was 38.0+/-17.5 days in the control group vs 66.0+/-18.6 days in the ALSS group (P less than 0.05). The survival time of end stage patients of the control group and the ALSS group was 18.0+/-4.0 days vs 26.0+/-2.5 days (P less than 0.01).</p><p><b>CONCLUSIONS</b>Multi ALSS treatment is more effective than the standard medicinal liver care treatment. Multi-ALSS treatment could increase survival time of patients suffering from acute liver failure or A on C liver failure, especially in their middle and end stages. It is important and necessary to treat these patients with ALSS.</p>

Preliminary study on determination of specific cellular immunity of patients with hepatitis B / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To evaluate an enzyme linked immunospot (ELISPOT) method for testing the specific cellular immunity of patients with hepatitis B and preliminarily investigate into the difference of cellular immunity in patients with various types of hepatitis B.</p><p><b>METHODS</b>The patients with acute hepatitis B, chronic hepatitis B liver cirrhosis, healthy persons with HBV vaccine immunization, healthy persons with past HBV infection and HBV naive persons were enrolled in this study. Their peripheral blood mononuclear cells were tested by ELISPOT to determine the number of gamma-interferon secreting cells.</p><p><b>RESULTS</b>The number of gamma-interferon secreting cells was significantly different between the patients with acute hepatitis B and those with chronic hepatitis B, and between the patients with acute hepatitis B and those with liver cirrhosis (P=0.0209 and P=0.0211).</p><p><b>CONCLUSION</b>The specific cellular immunity in the patients with hepatitis B could be evaluated by determining the number of gamma-interferon secreting cells with the method of testing their peripheral blood mononuclear cells by ELISPOT. The specific cellular immunity was stronger in the patients with acute hepatitis B than in those with chronic hepatitis B and liver cirrhosis.</p>

Follow up study on viruses associated with SARS among the SARS patients / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To study the existence status of the SARS-CoV, retrovirus, and the poliovirus in the bodies of the patients with SARS and the possible relationship between the three viruses and SARS.</p><p><b>METHODS</b>The clinical specimens of the nasopharyngeal swabs, sputum (or saliva), urine, fecal specimens were collected on three consecutive days from 8 patients with SARS 2 years after the recovery from SARS. SARS-CoV, reovirus and poliovirus RNA was detected by using reverse transcription (RT)-PCR; IgG antibody to the poliovirus type 1 and 3 and the antibody to SARS-CoV were determined using enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>All the specimens were negative for SARS-CoV and reovirus by RT-PCR, but the fecal specimens from 4 persons were positive for poliovirus. The sequences of these poliovirus were highly homologous to that of human poliovirus type 1 strain sabin 1 genome at nucleotide level, but back mutations have occurred in the primary attenuating mutation sites at nucleotide position 480 (G --> A) in the 5' UTR and the nucleotide position 2795 (A --> G). No SARS-CoV, reovirus, and poliovirus were found in the normal controls. Three serum specimens were positive for the antibody to SARS-CoV. The IgG antibody to poliovirus were detected in 4 SARS patients and 23 healthy persons. No positive results for antibody to SARS-CoV were detected in the 25 healthy persons.</p><p><b>CONCLUSION</b>The positive rate of the poliovirus antibody in the serum of SARS patients 2 years after recovery was significantly different from that of the normal controls, and the positive rate of poliovirus in the fecal specimens was still very high, and more importantly back mutations have occurred in the attenuating mutation sites at nucleotide position which plays an important role in the poliomyelitis.</p>

Characteristics of peripheral circulating lymphocyte subsets and their clinical implication in severe hapatitis patients with chronic HBV infection / 第二军医大学学报

Objective: To investigate the characteristics of peripheral circulating lymphocyte subsets in severe hepatitis patients with chronic HBV infection (SHPCHI). Methods: The numbers of circulating lymphocyte subsets, including CD3+, CD4+ and CD8+, NK cells (CD3- /CD16+ /CD56+), and NKT cells (CD3+ /CD16+ CD56+), were determined in SHPCHI (n=61),patients with chronic hepatitis B (CHB, n=21), patients with cirrhosis (LC, n=26) and healthy volunteers (n=10) by flow cytometry. The absolute values of each lymphocyte subset were calculated and statistically analyzed. Results: The absolute numbers of circulating CD3+, CD4+ and CD8+ T cells were significantly reduced in SHPCHI group compared with those in the other 3 groups (P<0.01 or P<0.05). There was a decreasing trend in the absolute numbers of peripheral CD3+, CD4+, CD8+ and NK cells in non-surviving SHPCHI compared with surviving SHPCHI,but the decrease was not statistically significant. Conclusion: SHPCHI has an disorderd cellular immune function, which might be related to the prognosis of SHPCHI.