Predictive value of the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score in the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure / 中华医学杂志(英文版)

Background@#As a large, prospective, multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score (COSSH-ACLFs), has been approved by some foreign scholars; however, its predictive value needs to be verified. This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF.@*Methods@#This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014. Spearman method was used to assess the correlation of COSSHACLFs with classical scores. Different COX multivariate regression models were used to confirm the relationship between COSSHACLFs and short-term prognosis in patients with HBV-ACLF, and stratified analysis was used to further verify the stability of this relationship. We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve (AUROC) and Z-test.@*Results@#A total of 975 patients with HBV-ACLF were screened, and 751 were analyzed (623 male and 128 female). COSSH-ACLFs was the highest in patients with end-stage ACLF, followed by those with middle- and early-stage ACLF (H = 211.8, P < 0.001). In the fully adjusted model, COX multivariate regression analysis revealed that COSSH-ACLFs (as a continuous variable) was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days (hazard ratio [HR]: 1.37 [1.22, 1.53], P < 0.001) and 90 days (HR: 1.43 [1.29, 1.58], P < 0.001). The same trend could be observed in the crude model and minimally adjusted model. The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792, respectively, indicating a stronger predictive accuracy than those of classic models.@*Conclusions@#COSSH-ACLFs, with a superior predictive accuracy compared with other classical scores, can strongly predict shortterm prognosis in Chinese patients with HBV-ACLF.

Predictive value of the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score in the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure / 中华医学杂志(英文版)

BACKGROUND@#As a large, prospective, multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score (COSSH-ACLFs), has been approved by some foreign scholars; however, its predictive value needs to be verified. This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF.@*METHODS@#This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014. Spearman method was used to assess the correlation of COSSH-ACLFs with classical scores. Different COX multivariate regression models were used to confirm the relationship between COSSH-ACLFs and short-term prognosis in patients with HBV-ACLF, and stratified analysis was used to further verify the stability of this relationship. We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve (AUROC) and Z-test.@*RESULTS@#A total of 975 patients with HBV-ACLF were screened, and 751 were analyzed (623 male and 128 female). COSSH-ACLFs was the highest in patients with end-stage ACLF, followed by those with middle- and early-stage ACLF (H = 211.8, P < 0.001). In the fully adjusted model, COX multivariate regression analysis revealed that COSSH-ACLFs (as a continuous variable) was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days (hazard ratio [HR]: 1.37 [1.22, 1.53], P < 0.001) and 90 days (HR: 1.43 [1.29, 1.58], P < 0.001). The same trend could be observed in the crude model and minimally adjusted model. The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792, respectively, indicating a stronger predictive accuracy than those of classic models.@*CONCLUSIONS@#COSSH-ACLFs, with a superior predictive accuracy compared with other classical scores, can strongly predict short-term prognosis in Chinese patients with HBV-ACLF.

Clinical analysis of liver transplantation for autoimmune hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To describe the outcomes and recurrence of autoimmune hepatitis (AIH) after liver transplantation.</p><p><b>METHODS</b>Clinical data of 16 patients with AIH who underwent liver transplantation were analyzed retrospectively. The postoperative cumulative survival rate of the patients was calculated. The postoperative rejections and AIH recurrence were analyzed. The Kaplan-Meier method was used for statistical analysis of survival.</p><p><b>RESULTS</b>All patients were female, with an average age of 52.6 years (range: 41-66 years), and an average MELD score of 21.4. According serological analysis, 15 patients were AIH type 1 and 1 patient was AIH type 2. Three patients died, including 2 of pulmonary infection and 1 of graft dysfunction.The 1-, 2-and 5-year cumulative survival rates were 93.8%, 87.1% and 79.1%, respectively. Five cases (31.3%) of recurrent AIH were diagnosed based on histological evidence. Acute rejection occurred in 6 (37.5%) patients, and de novo HBV infection occurred in 1 (6.3%) patient.</p><p><b>CONCLUSION</b>Liver transplantation is an effective treatment for end-stage AIH. Recurrence and rejection were commonly associated with AIH, but did not negatively impact patient survival.</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>

The clinical characteristics of hepatic failure with aspergillosis / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To study the clinical characteristics of hepatic failure with aspergillosis.</p><p><b>METHODS</b>The data of hepatic failure patients with fungal infection hospitalized in our hospital form January 1985 to June 2006 were collected. This research mainly focused on the clinical characteristics of the patients co-infected with aspergillosis.</p><p><b>RESULTS</b>The occurrence of aspergillosis was 20.5% (104 cases) among 507 hepatic failure patients with fungal infection. Compared with other fungal infection in hepatic failure patients, the effective rate of antifungal therapy and the improvement rate of underlying disease were worse in patients with aspergillus infection (36.5% vs 57.8%, P = 0.000; 26.0% vs 36.7%, P = 0.049). Aspergillus fumigatus was the most common species among 108 fungal species. The species next to Aspergillus fumigatus were Aspergillus niger and Aspergillus flavus. The mainly infected organ was lung and its clinical manifestation was atypical. Liver function could be improved with effective anti-fungus therapy.</p><p><b>CONCLUSIONS</b>Diagnosis and treatment of aspergillosis is difficult in hepatic failure patients co-infected with aspergillosis. Early and effective antifungal therapy is helpful to the recovery of liver function in the hepatic failure patients suspected with aspergillosis co-infection.</p>

Association between HBV genotype and chronic/severe liver disease with HBV infection in Chinese patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the association between HBV genotype and chronic/severe liver disease with HBV infection in Chinese patients.</p><p><b>METHODS</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 between various clinical types of HBV infection and liver function and virological markers between various HBV genotyping were analyzed.</p><p><b>RESULTS</b>The genotype B, C, BC combinations, D of 2922 patients with HBV infection accounted for 15.9%, 83.5%, 0.41%, 0.21% respectively. The ratio of genotype B in acute hepatitis group was higher (P = 0.003), which the ratio of genotype C in the cirrhosis group and the hepatocellular carcinoma group was higher (P = 0.000, 0.000). The difference in ratio of genotype C was not statistically significant between acute-on-chronic liver failure group and chronic hepatitis group. HBeAg-positive rate, viral load and liver function markers of B, C genotype group in acute hepatitis group and chronic hepatitis group were not significant different. HBeAg-positive rates of genotype C in acute-on-chronic liver failure group, cirrhosis group, hepatocellular carcinoma group were higher than that of genotype B (P = 0.000, 0.024, 0.003). Viral load of genotype C in hepatocellular carcinoma group was higher than that of genotype B (P = 0.025). Cholinesterase levels of genotype C in the acute-on-chronic liver failure group and the hepatocellular carcinoma group was lower than that of genotype B (P = 0.0004, 0.02).</p><p><b>CONCLUSION</b>There were HBV genotype B, C, B/C combinations and D in Chinese patients with HBV infection, with genotype B and C being the major ones. Compared with HBV genotype B, genotype C in Chinese patients with HBV infection was more likely to chronic infection, evolved to cirrhosis and hepatocellular carcinoma, but genotype difference was not observed in occurrence of acute-on-chronic liver failure. Genotype was not significant effect in acute and chronic hepatitis B, but HBeAg-positive rate/viral load was higher and liver damage was more severe in severe and end-stage genotype C HBV infection patients.</p>

Analysis the relationship of HBV BCP A1762T/G1764A double mutation with HBV related acute on chronic liver failure / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To analysis the relationship between HBV BCP A1762T/G1764A double mutation with acute on chronic liver failure (ACLF).</p><p><b>METHODS</b>HBV BCP A1762T/G1764A double mutation was detected in 166 HBV chronic infection patients by nested PCR and direct DNA sequencing. The mutation rate was compared among the patients with different disease course.</p><p><b>RESULTS</b>Among 166 patients, 45 patients, 45 patients, 49 patients and 27 patients were diagnosed as chronic hepatitis B (CHB), liver cirrhosis (LC), ACLF and hepatocellular carcinoma (HCC), respectively. A1762T/G1764A double mutation rate was 40.0% (18/45), 84.4% (38/45), 73.5% (36/49) and 92.6% (25/27) respectively in different groups. However, A1762T/G1764A double mutation rate has no difference between ACLF based on CHB and LC (P = 0.502) and between patients with HBeAg positive and negative (P = 0.735). HBV DNA level (log) of patients with A1762T/G1764A double mutation was 5.68 +/- 1.36, lower than but having no significant statistic difference compared to patients without the double mutation (6.14 +/- 1.81, P = 0.075).</p><p><b>CONCLUSION</b>A1762T/G1764A double mutation has a close relationship with the progress of HBV-infection diseases, but is not specific to patients with ACLF. And patients with BCP double mutation have similar HBV DNA levels and HBeAg status with patients without the double mutation.</p>

Rescue of dendritic cells malfunction and loading with HBV proteins in patients with chronic hepatitis B in vitro / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate dendritic cell (DC) malfunctions in patients with chronic hepatitis B (CHB) and try some means to restore the function in vitro.</p><p><b>METHODS</b>Twelve CHB patients and 10 healthy people were enrolled in the study. Phenotype analysis and allogeneic mixed lymphocyte reaction (AMLR) assay of DC from these subjects were made. Enzyme-linked ELISpot method for detecting IFN-gamma-producing CD8 (+) T cells were used to evaluate the efficacy of DC loaded in vitro with HBsAg or HBcAg.</p><p><b>RESULTS</b>DC from patients had a lower expression of co-stimulatory molecules and impaired AMLR capacity, but was restored partially by cytokine cocktail in vitro. Mature DC loaded with HBsAg or HBcAg showed a greater capacity for IFN-gamma-production than immature DC.</p><p><b>CONCLUSION</b>Malfunction of DC from CHB patients may be rescued by a cocktail of cytokines, and therapeutic DC vaccines loaded with HBV protein might be helpful to treat CHB patients.</p>

Therapeutic effect of autologous cytokine-induced killer cells on patients with liver cirrhosis caused by HBV infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of autologous cytokine-induced killer cells (CIK) on HBV DNA positive patients with liver cirrhosis.</p><p><b>METHODS</b>HBV DNA positive 33 patients with cirrhosis were treated with CIK. Before and after cultured in vitro and post-treatment, CD3+, CD3+CD4+, CD3+CD8+, CD3+CD56+ cells, mDC and pDC were detected by flow cytometry. The indexes of virus and liver function were compared between pre- and post-treatment.</p><p><b>RESULTS</b>CD3+, CD3+CD8+ cells and CD3+CD56+ cells were higher after cultured in vitro and after transfused back than those before culture (91.5 +/- 10.3, 74.4 +/- 9.9 vs. 67.9 +/- 12.8; 60.9 +/- 15.5, 37.3 +/- 15.1 vs. 27.9 +/- 10.9; 18.4 +/- 11.7, 14.5 +/- 7.5 vs. 10.6 +/- 7.1). The percentages of mDC and pDC also increased after-treatment vs. pre-treatment (0.54 +/- 0.18 vs. 0.70 +/- 0.29; 0.26 +/- 0.13 vs. 0.41 +/- 0.25). HBV DNA became undetectable in 12 patients and decrease exceeded 100 times in 4 patients after treatment. HBeAg became undetectable in 10 of 14 patients who were HBeAg positive pretreatment patients, among them 2 patients had HBeAb sero conversion. The liver function was improved after treatment. All patients tolerated the treatment.</p><p><b>CONCLUSION</b>CIK treatment can increase immune effector cells and has some antiviral effect and is safe.</p>

Retrospective study of liver failure complicated with bacterium and fungous infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study clinic character of liver failure complicated with bacterium and fungous infection.</p><p><b>METHODS</b>The patients with liver failure complicated with bacterial and fungous infection who were treated in our hospital from January 1986 to June 2006 were studied. All patients had clinical manifestation and positive of bacterium. The data were statistical analysis.</p><p><b>RESULTS</b>507 patients diagnosed with fungous infection were found from January 1986 to June 2006 in which 132 patients were diagnosed with bacterial and fungous infection. There were 85 patients (64.39%) with chronic severe hepatitis and 40 patients (30.3%) with decompensation cirrhosis. Bacterial infection happened in 153 cases in which the rate of nosocomial infections was 54.90%. 204 bacterial strains were separated in which 143 strains (70.10%) were gram-negative bacterium and 61 (29.90%) strains were gram-positive bacterium. The main sites of bacterial infection were abdominal cavity (122 cases) and lung (30 cases). Fungous infection happened in 143 cases in which the rate of nosocomial infections was 86.71%. 155 fungous strains were separated in which 90 strains (58.06%) were Candida albicans, 17 strains (10.97%) were Aspergillus fumigatus and 25 (16.13%) strains were non-Candida albicans. The main sites of fouguns infection were lung (94 cases) and mouth (53 cases). 84 patients (63.64%) were ineffective and died after treatment.</p><p><b>CONCLUSION</b>The patients with decompensation cirrhosis and chronic severe liver hepatitis were easy to be infected by bacterial and fungous. the rate of fungous nosocomial infections is higher than that of bacterium. The prognosis is bad in patients who had secondary fungous infection.</p>

Cytokines secretion by peripheral blood mononuclear cells from hepatitis C patients after stimulation with synthetic peptides at the highly variable region / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>Test the cytokines secretion by peripheral blood mononuclear cells (PBMC) from hepatitis C patients after stimulation with highly variable region (HVR1) synthetic peptides.</p><p><b>METHODS</b>ELISA was used to test the cytokines secretion, flow cytometry to group the proliferated cells, and the antigenicity of synthetic peptide was predicted by the computer modeling.</p><p><b>RESULTS</b>(1)There were PBMC proliferation when stimulated by HVR1 antigen synthetic peptides. (2) There was a rise of IFN-gamma, IL-4 and IL-10. But no rise of IL-2 and TNF-gamma was found. (3) The proliferated cells were mainly CD4+ lymphocytes.</p><p><b>CONCLUSION</b>PMBC from hepatitis C patients tend to secret Th2 cytokines after stimulation with HVR1 designed by the authors.</p>

Clinical analysis of 77 liver failure patients with nosocomially infected septicemia / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics and preventive measures of liver failure with nosocomial septicemia.</p><p><b>METHODS</b>Retrospective analysis of nosocomial septicemia seen between 2001 and 2002 was carried out in our hospital.</p><p><b>RESULTS</b>Incidence of nosocomial septicemia was 0.61%, mortality was 14.29%, the main pathogen was Escherichia coli, the drug resistance occurred in most pathogens to the commonly used antibiotics.</p><p><b>CONCLUSION</b>In order to reduce nosocomial septicemia, antibiotics should be used rationally, should be paid attention to bacterial culture and antibiotic sensitivity, and preventive measures should be taken.</p>

Treatment of patients with chronic hepatitis B virus infect ion with lamivudine combined with famciclovir / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of combined treatment with lamivudine and famciclovir on chronic hepatitis B virus (HBV) infection.</p><p><b>METHODS</b>Ninety patients with chronic HBV infection were divided into 3 groups. Group one had 28 patients and was treated with combination of lamivudine (0.1 g/d, PO) and famciclovir (1.5 g/d,PO) for 24 weeks. Group two and three had 30 and 32 cases, respectively, and were treated with lamivudine 100 mg/day PO and famciclovir (1.5 g/d,PO) alone. All the patients had positive markers of HBsAg, HBeAg and anti-HBcAg in serum assayed by ELISA and of HBV DNA tested by PCR.</p><p><b>RESULTS</b>Three strategies of treatment had no different effects on the change of patients' ALT levels. The serum HBV DNA became negative after treatment in 89.3% (25/28) of patients treated with combination of lamivudine and famciclovir, 66.7% (20/30) of patients treated with lamivudine, and 40.6% (13/32) of patients treated with famciclovir. The rate of serum HBeAg loss in 3 groups were 28.6% (8/28), 23.3% (7/30) and 21.9% (7/32), respectively.</p><p><b>CONCLUSIONS</b>The combination treatment of lamivudine and famciclovir for chronic HBV infection is safer than and superior to that of either drug alone.</p>