中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

2014 No. 10

Display Method:
Editorial
The definition and natural history of severe exacerbation of hepatitis B
Guo Wei, Li WeiNa, Ning Qin
2014, 30(10): 967-969. DOI: 10.3969/j.issn.1001-5256.2014.10.001
Abstract:

Despite different opinions on its definition and classification in the past, a consensus has gradually been reached regarding the naming, classification, and clinical diagnosis of liver failure. The classification of liver failure is described, and the definition and natural history of severe exacerbation of hepatitis B are summarized. Antiviral treatment and artificial liver support in the early stage are beneficial for clinical outcomes and prognosis.

Therapeutic guidelines
Chinese consensus on pancreatic cancer diagnosis and treatment (2014 version)
The Chinese Society of Clinical Oncology Pancreatic Cancer Expert Committee;
2014, 30(10): 970-980. DOI: 10.3969/j.issn.1001-5256.2014.10.002
Abstract:
Discussions by experts
Cytokine storm and liver failure
Chen Zhi, Zhu HaiHong, Yang Ying
2014, 30(10): 981-983. DOI: 10.3969/j.issn.1001-5256.2014.10.003
Abstract:
Cytokine storm plays an important role in the pathogenesis of liver failure. It is closely related to hepatocyte necrosis in the clinical course and the prognosis of this disease. With Kupffer cells as a clue, it is elucidated that related cells and cytokines influence each other and jointly function in the development and progression of liver failure, leading to serious liver tissue damage and necrosis. Cytokine-based research can help improve early diagnosis, disease assessment, and individualized treatment for liver failure.
Immune-mediated liver failure
Wang XiaoJing, Zhang XiaoPing, Ning Qin
2014, 30(10): 984-991. DOI: 10.3969/j.issn.1001-5256.2014.10.004
Abstract:
The primary causative factors of liver failure include direct damage and immune-mediated liver injury. Increasing evidence suggests that immune-mediated injury plays a pivotal role in the pathogenesis of liver failure. The new concepts concerning the mechanisms of immune-mediated liver injury in liver failure are reviewed with relevant basic and clinical studies in both humans and animals. The innate and adaptive immunity, particularly the interaction of various immune cells and molecules, as well as apoptosis-related molecules, are discussed in detail.
Original articles_Liver failure
Logistic regression analysis of prognostic factors in 106 acute-on-chronic liver failure patients with hepatic encephalopathy
Cui YanPing, Liu FengHua, Shi QingFeng, Zhao HongKui, Wang SiKui
2014, 30(10): 992-995. DOI: 10.3969/j.issn.1001-5256.2014.10.005
Abstract:

Objective To analyze the prognostic factors in acute-on-chronic liver failure ( ACLF) patients with hepatic encephalopathy ( HE) and to explore the risk factors for prognosis. Methods A retrospective analysis was performed on106 ACLF patients with HE who were hospitalized in our hospital from January 2010 to July 2013. The patients were divided into improved group and deteriorated group. The univariate indicators including age, sex, laboratory indicators [total bilirubin ( TBil) , albumin ( Alb) , alanine aminotransferase ( ALT) , aspartate amino-transferase ( AST) , and prothrombin time activity ( PTA) ], the stage of HE, complications [persistent hyponatremia, digestive tract bleeding, hepatorenal syndrome ( HRS) , ascites, infection, and spontaneous bacterial peritonitis ( SBP) ], and plasma exchange were analyzed by chi-square test or t-test. Indicators with statistical significance were subsequently analyzed by binary logistic regression. Results Univariate analysis showed that ALT ( P = 0. 009) , PTA ( P = 0. 043) , the stage of HE ( P = 0. 000) , and HRS ( P = 0. 003) were significantly different between the two groups, whereas differences in age, sex, TBil, Alb, AST, persistent hyponatremia, digestive tract bleeding, ascites, infection, SBP, and plasma exchange were not statistically significant ( P >0. 05) . Binary logistic regression demonstrated that PTA ( b =-0. 097, P =0. 025, OR =0. 908) , HRS ( b =2. 279, P =0. 007, OR =9. 764) , and the stage of HE ( b = 1. 873, P = 0. 000, OR = 6. 510) were prognostic factors in ACLF patients with HE. Conclusion The stage of HE, HRS, and PTA are independent influential factors for the prognosis in ACLF patients with HE. Reduced PTA, advanced HE stage, and the presence of HRS indicate worse prognosis.

A simple scoring system for evaluating severity of HBV-related acute-on-chronic liver failure
Li XinYan, Huang ShuLin, Fang Liang, Lei RuiXiang, Ke WeiMin
2014, 30(10): 996-999. DOI: 10.3969/j.issn.1001-5256.2014.10.006
Abstract:

Objective To establish a simple scoring system for evaluating the severity of hepatitis B virus ( HBV) -related acute-on-chronic liver failure ( HBV-ACLF) . Methods A retrospective analysis was performed on the clinical data of 620 patients with HBV-ACLF who were divided into group I ( 500 patients) and group II ( 120 patients) . Seven clinical parameters, including hepatic encephalopathy, serum creatinine, prothrombin activity, serum total bilirubin, infection, dimension of liver, and maximum depth of ascites, were scored from 0-4 points for each patient according to the disease severity. The severity scoring system was established based on the total score of each patient in group I, with the cut-off point being determined. The established system was tested with group II. Results A severity scoring system was successfully developed based on chi-squared automatic interaction detector analysis of the total score of each patient in group I. There was a significant difference in the total score between the survival and death subgroups of the 500 patients ( t = 25. 78, P <0. 001) . The area under the ROC curve was 0. 963, suggesting a high validity of this scoring system. With the cut-off value of 9. 5, the sensitivity and specificity of this system were 0. 98 and 0. 83, respectively. The other 120 patients were divided into the poor prognosis ( score ≥10) and good prognosis subgroups ( score ≤9) based on the scoring system, with the mortality rates being 84.3% and 3.5%, respectively; there was a significant difference in mortality between the two subgroups ( χ2= 72. 2, P < 0. 001) . Conclusion This scoring system is simple, sensitive, and objective to evaluate the severity of HBV-ACLF.

Predictive value of Glasgow Prognostic Score system for mortality in patients with acute-on-chronic liver failure associated with hepatitis B
Li ShaoJun, Cheng JiaXi, Lu XiaoBo, Zhang LiJuan, Zhang YueXin
2014, 30(10): 1000-1004. DOI: 10.3969/j.issn.1001-5256.2014.10.007
Abstract:

Objective To assess the predictive value of Glasgow Prognostic Score ( GPS) system for mortality in patients with acute-on-chronic liver failure associated with hepatitis B ( HBV-ACLF) . Methods The clinical data of 437 patients who were diagnosed with HBV-ACLF and admitted to the Department of Infectious Diseases, The First Affiliated Hospital of Xinjiang Medical University, from April 2008 to April 2012 were retrospectively evaluated. Patients were grouped according to their GPS scores, and the mortality rates were compared between GPS groups. Continuous data in normal distribution were compared by t test between two groups and by F-test between three or more groups. Comparison of categorical data was made by chi-square test. COX proportional hazards regression was performed to identify clinical variables associated with overall survival during the follow-up period [30 ( 5-825) d]. Results The mortality rate of patients with HBV-ACLF was 68. 0% ( 297 cases) during the follow-up period. The group with higher GPS scores had significantly increased proportions of individuals with gastrointestinal bleeding, hepatic encephalopathy, and hepatorenal syndrome and higher Model of End-Stage Liver Disease scores ( P < 0. 05 across all variables) . COX proportional hazards regression analysis revealed the risk factors closely associated with the mortality of patients with HBV-ACLF, which included hepatic encephalopathy ( grade I-II vs absence of hepatic encephalopathy: hazard ratio, HR: 2. 520, 95% confidence interval, CI: 1. 479-4. 293, P = 0. 001; grade III-IV vs absence of hepatic encephalopathy: HR:3. 678, 95% CI: 1. 920-7. 047, P < 0. 001) , hepatorenal syndrome ( HR: 2. 374, 95% CI: 1. 452-3. 881, P = 0. 001) , gastrointestinal bleeding ( HR: 1. 616, 95% CI: 1. 153-2. 262, P = 0. 004) , antiviral therapy ( HR: 0. 668, 95% CI: 0. 518-0. 862, P = 0. 002) and the GPS ( 1 vs 0: HR: 2. 055, 95% CI: 1653-2. 702, P = 0. 001; 2 vs 0: HR: 4. 520, 95% CI: 3. 288-6. 932, P = 0. 007) . Conclusion The GPS system has a good predictive value for short-and long-term mortality in patients with HBV-ACLF. Elevated GPS is an independent risk factor for death in patients with chronic liver failure associated with hepatitis B.

Association of ERα gene polymorphism at position 29 with HBV-related acute-on-chronic liver failure
Zhou Ning, Zhang YueRong, Wei ShiFang, Wu LiYang, Li XiangLin, Sun MeiYing
2014, 30(10): 1005-1008. DOI: 10.3969/j.issn.1001-5256.2014.10.008
Abstract:

Objective To investigate the relationship between estrogen receptor alpha ( ERα) gene polymorphism at position 29 and hepatitis B virus ( HBV) -related acute-on-chronic liver failure ( HBV-ACLF) and the genetic pathogenesis of HBV-ACLF. Methods A total of 61HBV-ACLF patients, 79 patients with chronic hepatitis B ( CHB) , and 69 patients who automatically recovered from HBV infection were included in the study. The ERα gene polymorphism at position 29 was analyzed by polymerase chain reaction-restriction fragment length polymorphism. The allele frequency was calculated by gene counting, and Hardy-Weinberg equilibrium test was performed. Confounding factors were adjusted by unconditional logistic regression analysis. Comparisons of genotype frequency and allele frequency were made by chi-square test ( R × C) . Results The frequencies of TT genotype and T allele of ERα gene at position 29 were significantly higher in HBV-ACLF patients than in CHB patients (55.7% vs 31.6%, χ2=8. 194, P =0. 004; 77. 1% vs 54. 4%, χ2=15. 341, P <0. 001) , and the risk of worsening in HBV infection patients with T allele was 2. 811 times that in HBV infection patient with C allele ( OR =2. 811, 95% CI: 1. 662-4. 753) . The frequencies of TT genotype and T allele of ERα gene at position 29 were significantly higher in HBV-ACLF patients than in patients who recovered from HBV infection ( 55. 7% vs11. 6%, χ2=28. 849, P <0. 001; 77. 1% vs 32. 6%, χ2=51. 401, P <0. 001) , and the risk of worsening in HBV infection patients with T allele was 6. 938 times that in patients with C allele ( OR =6. 938, 95% CI: 3. 995-12. 050) . Conclusion TT genotype and T allele of ERα gene at position 29 might be the susceptibility gene for HBV-ACLF.

Meta-analysis of risk factors for posthepatectomy liver failure in patients with hepatocellular carcinoma
Yin TianSheng, Yi YaYang, Mao XiXian, Li DeWei
2014, 30(10): 1009-1014. DOI: 10.3969/j.issn.1001-5256.2014.10.009
Abstract:

Objective To investigate the risk factors for posthepatectomy liver failure ( PHLF) in patients with hepatocellular carcinoma ( HCC) and to provide a theoretical basis for the prediction and prevention of PHLF. Methods A meta-analysis was performed on the studies on risk factors for PHLF in HCC patients published in China from January 1990 to June 2013 by searching SinoMed, VIP, CNKI, and Wanfang Data and manual retrieval of related articles and references. Results A total of 11 studies involving 2859 patients treated with hepatectomy were included in the meta-analysis. The incidence of PHLF was significantly lower in Child-Pugh A patients than in the control group ( pooled OR = 6. 28, 95% CI: 4. 55-8. 65) . Patients with prealbumin levels less than 170 mg /dl had an increased incidence of PHLF ( pooled OR = 4. 96, 95% CI: 3. 03-8. 10) . Patients with cirrhosis had a higher incidence of PHLF than those without cirrhosis ( pooled OR = 4.14, 95%CI: 2.46-6.98) . Patients with an intraoperative blood loss less than 1000 ml had a lower incidence of PHLF than the control group ( pooled OR = 5. 62, 95% CI: 3. 46-9. 11) . The incidence of PHLF was lower in patients with a tumor diameter less than 10 cm and patients with an extent of resection less than hepatectomy than in the control group ( pooled OR = 2. 69, 95% CI: 1. 58-4. 57; pooled OR = 1. 64, 95% CI: 1. 12-2. 40) . Age ≥60 years and intraoperative blood transfusion increased the incidence of PHLF ( pooled OR = 1.73, 95% CI: 1.25-2.39; pooled OR = 3.79, 95% CI: 2.20-6.51) . Sex and hepatic inflow occlusion were not significantly associated with the development of PHLF ( P > 0. 05) Conclusion Advanced age, advanced preoperative Child-Pugh class, low prealbumin level, high intraoperative blood loss, large tumor diameter, large extent of hepatectomy, cirrhosis, and intraoperative blood transfusion are risk factors for the development of PHLF.

Clinical efficacy of plasma exchange therapy in treatment of liver failure
Zhang Lin, Zhao ShouSong
2014, 30(10): 1015-1019. DOI: 10.3969/j.issn.1001-5256.2014.10.010
Abstract:

Objective To investigate the clinical efficacy of plasma exchange ( PE) in the treatment of liver failure. Methods A retrospective analysis was performed on the clinical data of patients with liver failure who were treated from January 2012 to June 2013 in our hospital. Thirty-three patients in PE group received PE in addition to medical comprehensive treatment, and 30 patients in control group were treated with medical comprehensive treatment. Clinical symptoms, complications, and the changes in biochemical markers of liver function were observed after 2 weeks of treatment, post-treatment outcomes were evaluated by 3-month followed-up, and the influential factors for efficacy were analyzed. Experimental data were expressed as mean ± standard deviation, continuous data were compared by t test, and categorical data were analyzed by chi-square test or Fisher's exact test. Results Symptoms such as fatigue, poor appetite, and abdominal distension were significantly relieved after PE. Post-treatment serum alanine aminotransferase ( ALT) and total bilirubin ( TBil) levels were significantly lower compared with pre-treatment levels ( 390. 48 ± 536. 52 U /L vs 81. 03 ± 47. 58 U /L and 479. 27 ± 130. 01 μmol /L vs244. 64 ± 151. 05 μmol /L, P < 0. 005) , whereas post-treatment levels of albumin ( Alb) and cholesterol ( CHO) and prothrombin activity ( PTA) were significantly higher than those measured before the treatment ( 33.06 ±5.42 g/L vs 35.24 ±3.68 g/L, 2.50 ±1.24 mmol/L vs 3. 59 ± 0. 86 mmol /L, and 34. 16% ± 5. 33% vs 73. 98% ± 27. 23%, P < 0. 005) . No significant differences were identified between pre-and post-treatment levels of ALT, TBil, Alb, CHO, and PTA ( P > 0. 05) . Patients in PE group had a significantly higher improvement rate ( χ2= 8. 276, P < 0. 005) and a significantly lower mortality rate ( χ2= 13. 258, P < 0. 005) compared with the control group. The efficacy of PE was found to be correlated with pre-treatment TBil level, complications, bilirubin enzyme separation, and age ≥40 years ( P <0.05) . TBil and bilirubin enzyme separation were independent risk factors affecting the efficacy of PE ( P <0.05, OR =1.01 and8. 75) . Adverse reactions occurred in 8 cases during PE treatment, and disappeared after symptomatic treatment. Conclusion PE is a safe and effective treatment for liver failure, and holds promise for clinical application. TBil level and bilirubin enzyme separation are independent risk factors affecting the efficacy of PE.

Clinical effect of artificial liver support system on serum hs-CRP level in patients with hepatic failure
Dong DanDan, Yan YouQin
2014, 30(10): 1020-1022. DOI: 10.3969/j.issn.1001-5256.2014.10.011
Abstract:

Objective To evaluate the clinical effect of artificial liver support system ( ALSS) on serum high-sensitivity C-reactive protein ( hs-CRP) level and investigate the influence of the change in hs-CRP level on clinical prognosis among patients with hepatic failure.Methods Patients were recruited into three groups: group one included 60 patients who received ALSS due to hepatic failure; group two included 37 patients with hepatic failure without ALSS treatment; and group three included 37 patients with chronic hepatitis B. The serum levels of hs-CRP were measured in groups two and three, and in group one before and after ALSS treatment. Comparison of continuous data between groups was made by t test, and comparison of categorical data was made by chi-square test. Results The levels of hs-CRP in group one before treatment and in groups two and three were 12. 89 ± 9. 39, 12. 22 ± 9. 73, and 2. 83 ± 6. 79, respectively. No significant difference in hs-CRP level between group one and group two was observed ( P > 0. 05) . However, the hs-CRP level in group three was significantly different from those in group one and group two ( P < 0. 001) . The improvement rate in group one after ALSS treatment ( 78.3%) was significantly higher compared with that in group two ( 54.05%) ( χ2= 6. 315, P < 0. 05) . ALSS treatment ( t = 5. 179, P <0. 05) . ALSS treatment was selectively effective in a subgroup of patients and greatly decreased the hs-CRP level in these patients ( t =5. 344, P = 0. 000) , resulting in a significant difference from the patients who were unresponsive to ALSS treatment ( t = 2. 368, P =0. 038) . Conclusion Artificial liver support system can decrease the hs-CRP level in patients with hepatic failure. Serum level of hs-CRP can be used as a clinical indicator of disease progression and predict the clinical outcomes of ALSS in patients with hepatic failure.

Changes in distribution of cholinergic and nitrergic nerves in antrum of rats with liver failure
Zhu JinZhao, Rao JunWei, Lu: Yong, Li Huan
2014, 30(10): 1023-1026. DOI: 10.3969/j.issn.1001-5256.2014.10.012
Abstract:

Objective To observe the changes in gastric emptying and distribution of cholinergic and nitrergic nerves in the myenteric plexus of the antrum of rats with liver failure. Methods Forty Wistar rats were randomly divided into control group and liver failure model group. The gastric emptying of rats was evaluated using Dextran blue 2000 as an indicator. The cholinergic and nitrergic nerves in the myenteric plexus of the antrum were observed by acetylcholinesterase and NADPH-d histochemical staining and whole-mount preparation of the myenteric plexus and were then quantitatively analyzed. Continuous data were expressed as mean ± SD, and comparison between groups was made by t test. Results Compared with the control group, the liver failure model group had significantly reduced gastric emptying ( 163. 00 ± 25. 68 vs 100. 00 ±18. 93, P < 0. 01) , a significantly reduced number of positive cholinergic neurons ( with significantly thinner fibers) in the myenteric plexus of the antrum ( t = 3. 201, P < 0. 01) , and a significantly increased number of positive nitrergic neurons and fibers ( t = 2. 912, P < 0. 01) . Conclusion For rats with liver failure, declining gastric function is associated with a reduced number of cholinergic nerves and an increased number of nitrergic nerves in the myenteric plexus of the antrum.

Functional study on two artificial liver bioreactors with collagen gel
Xu Bing, Wu LinLan, Wei JianWei, Huang SuQin, Chen Yi, Zhao ZhiPing, Jiang XiaoZhi, Zheng DengZi, Yang MeiYu
2014, 30(10): 1027-1030. DOI: 10.3969/j.issn.1001-5256.2014.10.013
Abstract:

Objective To improve the hollow fiber bioreactor of artificial liver. Methods Rat hepatocytes mixed with collagen solution were injected into the external cavity of a hollow fiber reactor to construct a bioreactor of hepatocytes suspended in collagen gel ( group Ⅰ) .Other rat hepatocytes suspended in solution were injected into the external cavity of a hollow fiber reactor with a layer of collagen on the wall of the external cavity to construct a bioreactor of collagen layer and hepatocytes ( group Ⅱ) . For each group, the culture solution circulated through the internal cavity of the hollow fiber bioreactor; the bioreactor was put in a culture box for 9 d, and the culture solution in the internal cavity was exchanged for new one every 24 h; the concentrations of albumin ( Alb) , urea, and lactate dehydrogenase ( LDH) in the culture solution samples were measured to examine the hepatocyte function of the bioreactor. Statistical analysis was performed using SPSS13. 0. Continuous data were expressed as mean ± SD, and comparison between groups was made by paired t test. Results For groups Ⅰand Ⅱ, Alb levels reached peak values on day 3 of culture ( 1. 41 ± 0. 08 g /L and 0. 65 ± 0. 05 g /L) ; from day 3 to 9, group I had a significantly higher Alb level than group Ⅱ ( t > 7. 572, P < 0. 01) . For groups Ⅰ and Ⅱ, urea levels reached peak values on days 3 and 5 of culture ( 1. 73 ± 0. 14 mmol /L and 1. 56 ± 0. 18 mmol /L) ; from days 5 to 9, group I had a significantly higher urea level than group Ⅱ ( t> 8. 418, P < 0. 01) . For groups Ⅰ and Ⅱ, LDH levels reached peak values on day 9 of culture ( 32. 03 ± 9. 13 U /L and 70. 17 ± 25. 28 U / L) ; from days 1 to 9, group I had a significantly lower LDH level than group Ⅱ ( t > 5. 633, P < 0. 01) . Therefore, the bioreactor of hepatocytes suspended in collagen gel ( group Ⅰ) showed a better hepatocyte function and less hepatic enzyme leakage compared with the bioreactor of collagen layer and hepatocytes ( group Ⅱ) . Conclusion Hepatocytes suspended and immobilized in collagen gel might be more suitable for construction of a hollow fiber bioreactor of artificial liver.

Original articles_Viral hepatitis
Clinical efficacy of combined treatment with entecavir and adefovir dipivoxil for lamivudine-resistant chronic hepatitis B
Bao Jun, Liang JunCai, Gong Li, Chen XiaoXiao
2014, 30(10): 1031-1034. DOI: 10.3969/j.issn.1001-5256.2014.10.014
Abstract:

Objective To evaluate the efficacy and safety of the combined therapy with entecavir ( ETV) and adefovir dipivoxil ( ADV) in patients with lamivudine ( LAM) -resistant chronic hepatitis B ( CHB) . Methods A total of 45 patients who were diagnosed with LAM-resistant CHB and admitted to the Kunshan People's Hospital from May 2011 to May 2013 were recruited in this study and randomly divided to two groups. The treatment group included 23 CHB patients who received the combined therapy with ETV and ADV. The control group included 22 CHB patients who received the combined therapy with LAM and ADV. The changes in levels of HBV DNA, alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , total bilirubin ( TBil) , albumin ( Alb) , and HBV serum markers before and after 4, 12, 24, and 48 weeks of treatment, as well as the rate of mutations other than that at rtM204 I after 48 weeks of treatment, were measured in both groups. Comparison of continuous data between groups was made by t test, and comparison of categorical data by fourfold table chi-square test. Results The levels of ALT and AST in the treatment group were significantly lower than those in the control group after 4 and 12 weeks of treatment ( t = 3. 124, 5. 271, 4. 476, 5. 125, all P < 0. 01) , as well as 24 and 48 weeks of treatment ( t = 2. 240, 2. 307, 2. 886, 2. 908, all P < 0. 05) . The serum HBV DNA clearance rates in the treatment group after 4, 12, 24, and 48 weeks of treatment were73. 9%, 86. 8%, 95. 7%, and 100%, respectively, all of which were significantly higher than those in the control group ( χ2= 11. 79, 5. 75, 10. 29, 5. 89, respectively, all P < 0. 05) . However, there was no significant difference in the HBeAg seroconversion rate among HBeAg-positive patients between the two groups. No mutations other than that at rtM204 I were found in the treatment group, while four new mutations were detected in the control group ( χ2= 4. 59, P < 0. 05) . Conclusion The combined therapy with ETV and ADV has good therapeutic effect in treating LAM-resistant CHB patients, and the clinical application is highly recommended.

Zhang Ying, Jia JiDong
2014, 30(10): 1035-1038. DOI: 10.3969/j.issn.1001-5256.2014.10.015
Abstract:
Objective To investigate the changes in serum leptin and adiponectin levels and their significance in patients with chronic hepatitis B virus ( HBV) infection. Methods One hundred and twenty-five patients with chronic HBV infection ( 44 HBeAg-positive cases, 31 HBeAg-negative cases of chronic hepatitis B, 23 chronic HBV carriers, and 27 inactive HBsAg carriers) were recruited in the present study. Fifty-five healthy people served as the control group. Blood samples were collected at 8 to 9 AM of the next morning after overnight fasting. Blood glucose, blood lipids, renal and liver function parameters, fasting insulin, serum HBV markers, and HBV DNA concentration were determined, and HOMA-IR was calculated. Serum levels of leptin and adiponectin were measured by ELISA. Continuous data were expressed as mean ± SD, and Student's t-test, analysis of variance, linear regression analysis, and multiple regression analysis were applied in the analysis of all experimental data. Results There were no significant differences in serum levels of leptin and adiponectin between patients with chronic HBV infection and the control group ( P = 0. 480; P = 0. 321) , even after stratification by gender ( males: P =0. 210 /0. 895; females: P = 0. 404 /0. 066) . After patients with chronic HBV infection were divided into subgroups by HBeAg status, HBV DNA, or ALT level, there were no significant differences in serum levels of leptin and adiponectin between groups ( leptin: P = 0. 820 /0. 296 /0. 212; adiponectin: P = 0. 268 /0. 760 /0. 224) . Conclusion For patients with chronic HBV infection, infection status and viral replication level are not significantly correlated with serum levels of leptin and adiponectin.
HBV genotype distribution and its relationship with serum HBV DNA level and HBeAg expression among patients with chronic hepatitis B in southern Zhejiang Province, China
Zhou LianLian, Shen Mo, Zhou Ping, Zhou Wu, Lin XiangYang
2014, 30(10): 1039-1041. DOI: 10.3969/j.issn.1001-5256.2014.10.016
Abstract:
Objective To analyze the hepatitis B virus ( HBV) genotype distribution among chronic hepatitis B patients in southern Zhejiang Province, China, and to explore the relationship of HBV genotype with serum HBV DNA level and HBeAg expression. Methods Serum samples were collected from 161 patients positive for HBV DNA who visited our hospital from June 2011 to March 2012. Sequence-specific primer PCR was used for the HBV genotyping; real-time quantitative PCR was used to quantify HBV DNA ( copies /ml) ; ELISA was used to detect HBeAg. After logarithmic transformation was performed on HBV DNA levels so that the data were in normal distribution, the relationship between HBV genotype and HBeAg positive rate was analyzed by chi-square test, and the difference in HBV DNA level between patients with B and C genotypes was analyzed by t test. Results Of the 161 patients, 41 ( 25. 5%) had B genotype, 118 ( 73. 3%) had C genotype, and 2 ( 1. 2%) had B /C mixed genotype. The HBV DNA level and HBeAg positive rate for patients with C genotype were5. 84 ± 1. 40 log10 copies /ml and 64. 4%, respectively, higher than those for patients with B genotype ( 5. 49 ± 1. 33 log10 copies /ml and 53.7%) . Conclusion In southern Zhejiang Province, C genotype is the predominant genotype of HBV, followed by B genotype. Both HBV DNA level and HBeAg positive rate are higher in patients with C genotype than in those with B genotype. C genotype is closely associated with the development of liver cirrhosis.
Evaluation and selection of indirect ELISA and sandwich ELISA kits for anti-HCV detection
Li YongZhen, Zhen ZhiJun
2014, 30(10): 1042-1044. DOI: 10.3969/j.issn.1001-5256.2014.10.017
Abstract:
Objective To compare the sensitivity and specificity between indirect enzyme-linked immunosorbent assay ( ELISA) and double-antibody sandwich ELISA kits produced in China and to select the best ELISA kit. Methods Samples for evaluation included 60 serum plates and 40 serum samples positive or weakly positive for antibody to hepatitis C virus ( anti-HCV) which were confirmed by recombinant immunoblot assay. These samples were tested with a sandwich ELISA kit and three indirect ELISA kits, all of which were produced in China. Comparison between ELISA kits was made by paired chi-square test; comparison of false negative rate was made by R ×C contingency table test. Results The sensitivities of three indirect ELISA kits and a sandwich ELISA kit were 90. 2%, 78. 0%, 95. 1%, and 97. 6%, respectively, and the specificities were 78. 1%, 72. 6%, 94. 1%, and 100%, respectively. The sandwich ELISA kit had a 4-8 times higher sensitivity than indirect ELISA kits. The R × C contingency table test revealed significant differences in false negative rate between ELISA kits and combinations of ELISA kits ( χ2= 29. 898, P < 0. 05) . Conclusion Sandwich ELISA kit has higher sensitivity and specificity than indirect ELISA kits. Combined use of sandwich ELISA and indirect ELISA kits can significantly reduce the false negative rate and effectively prevent missed anti-HCV detection.
Original articles_Liver fibrosis and liver cirrhosis
A comparative study of FibroScan and B ultrasound in diagnosis of liver fibrosis
Liu LingFeng, Lu HaiYing, Yu YanYan, Wu ChiHong, Tian XiuLan
2014, 30(10): 1045-1049. DOI: 10.3969/j.issn.1001-5256.2014.10.018
Abstract:

Objective To compare the diagnostic performances of FibroScan ( FS) and B ultrasound for liver fibrosis and assess the relationship between the two methods. Methods The clinical data of 432 patients who were admitted to our institution between October 2012 and February 2014 were retrospectively analyzed. Of them, 305 had chronic hepatitis B virus infection, 96 had chronic hepatitis C virus infection, and 31 had primary biliary cirrhosis. FS values and parameters measured by B ultrasound including the thickness of left and right liver lobes, the diameter of the portal vein, spleen thickness, spleen length, the diameter of the splenic vein, and variables describing vascular morphology of the liver were recorded. Additionally, the incidence rates of ascites, fatty liver disease, gallbladder diseases, and liver cirrhosis were also reviewed. The correlations between FS value and the parameters were explored using the Spearman rank correlation test and multiple linear regression model. Patients were categorized based on FS values; parameters were compared between the groups by use of Kruskal-Wallis H test or Mann-Whitney U test. Results FS value was positively correlated with the thickness of left liver lobe, spleen thickness and length, the diameter of the portal vein, the diameter of the splenic vein, liver surface smoothness, parenchymal echo, vascular morphology, ascites ( presence or absence) , and liver cirrhosis ( presence or absence) ( rs= 0. 249-0. 543, P < 0. 05 for all) . Furthermore, positive correlations were also observed between these parameters and the stage of liver fibrosis as determined based on FS values ( rs= 0. 229-0. 541, P < 0. 05 for all) . Multiple linear regression analysis identified liver surface smoothness, thickness of the left liver lobe, ascites, and diameter of the portal vein as independent predictive factors for FS value ( t = 5. 123, 3. 703, 3. 113, and 2. 985, P <0. 05 for all) . FS values were 9. 573 ± 9. 490 kPa, 16. 339 ± 11. 359 kPa, and 27. 688 ± 18. 676 kPa in the three groups with liver echo enhancement, rough echo, and nodular echo, respectively; differences between the groups were significant ( χ2= 98. 469, P = 0. 000) .Conclusion There are reliable correlations between FS value and parameters measured by B ultrasound. The diagnostic performance of FibroScan for liver fibrosis is more accurate and objective than that of B ultrasound.

Strengthening self-management improves treatment compliance and outcome in hepatitis B patients with decompensated cirrhosis treated with entecavir
Cui YuHua, Wei XiaoJuan, Lin HuiMei
2014, 30(10): 1050-1052. DOI: 10.3969/j.issn.1001-5256.2014.10.019
Abstract:
Objective To investigate the effect of strengthening self-management on the treatment compliance and outcome in hepatitis B patients with decompensated cirrhosis treated with entecavir. Methods A total of 120 hepatitis B patients with decompensated cirrhosis, who received antiviral therapy with entecavir in our hospital from January 2010 to January 2012, were randomly divided into control group ( n= 60) and intervention group ( n = 60) . Both groups received routine nursing care; in addition, regular telephone follow-up was performed for the intervention group to provide guidance for the self-management during the comprehensive prevention and treatment of decompensated cirrhosis. The two groups were compared in terms of withdrawal rate, rehospitalization rate, hepatitis B virus ( HBV) DNA negative conversion rate, incidence of primary liver cancer, and mortality one year later. Continuous data were analyzed by t test, and categorical data by chi-square test or Fisher's exact test. Results The withdrawal rate and rehospitalization rate in the intervention group were 0 and 18. 3%, respectively, versus 8. 3% and 35% in the control group ( P < 0. 05 for both) . The HBV DNA negative conversion rate, incidence of primary liver cancer, and mortality in the intervention group were 90%, 3. 3%, and 5. 3%, versus 88. 3%, 5%, and 6. 7% in the control group ( P >0.05 for all) . Conclusion Strengthening self-management, as well as regular health education, can improve treatment compliance and promote recovery in hepatitis B patients with decompensated cirrhosis treated with entecavir.
Proteome analysis of liver nonparenchymal cells from rats with alcoholic liver fibrosis
Zhang LiJun, Jia XiaoFang, Wu DaGe, Liu XiaoQian, Huang Yan, Zhang JiaoLi, Cheng NengNeng
2014, 30(10): 1053-1059. DOI: 10.3969/j.issn.1001-5256.2014.10.020
Abstract:
Objective The development of alcoholic liver fibrosis ( ALF) is a complex process involving both parenchymal and nonparenchymal cells. The knowledge about the proteome of liver nonparenchymal cells ( NPCs) in response to ethanol is limited. This paper aims to investigate the regulatory effect of alcohol on the protein expression in liver NPCs during liver fibrosis development and to provide new clues for understanding the molecular mechanism of liver fibrosis. Methods Rats were treated with ethanol by gastric administration to establish a liver fibrosis model. The pathological changes in the liver were evaluated by James staining. Liver NPCs were enriched by Percoll density gradient centrifugation, and proteins were extracted from NPCs by two-dimensional gel electrophoresis ( 2DE) and stained by Coomassie Brilliant Blue G-250. The differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry ( LC-MS / MS) . Some of the differentially expressed proteins were verified by real time RT-PCR and Western blot. The protein spots on 2DE gels were analyzed by two sample t-test. The RT-PCR results were statistically analyzed by Mann-Whitney test. Results A rat model of ALF was established. Among the NPCs purified by Percoll density gradient centrifugation, lymphocytes, Kupffer cells, and endothelial cells were enriched for 1. 5, 3. 2, and 3. 7 times, respectively. More than 800 protein spots were detected by 2DE, and there were 26 proteins with more than 2-fold increases or decreases in expression; 21 non-redundant proteins were identified by LC-MS /MS and real-time RT-PCR analysis of 7 of these proteins showed that the mRNA levels of ANXA3, CES3, ATPA and NDUFV2 were in accordance with the proteome analysis results. Conclusion This study detected and identified a group of differentially expressed proteins related to ALF. Our work might offer some new clues to understand the mechanism of ALF.
Original articles_Hepatopancreatobiliary tumor
Application of hepatectomy without hepatic blood flow occlusion in treatment of primary liver cancer
Chen Kai, Qiu FuNan, Tian YiFeng, Lai ZhiDe, Zhou SongQiang, Yan MaoLin, Wang YaoDong
2014, 30(10): 1060-1063. DOI: 10.3969/j.issn.1001-5256.2014.10.021
Abstract:

Objective To investigate the effects of hepatectomy without hepatic blood flow occlusion ( HBFO) on the liver function and postoperative recovery in patients with primary liver cancer. Methods Eighty patients with primary liver cancer who underwent hepatectomy in our hospital from June 2010 to June 2013 were divided into three groups: first porta hepatis control ( Pringle) group ( n = 24) , hemihepatic vascular control ( HVC) group ( n = 24) , and non-HBFO group ( n = 32) . The operation time, intraoperative blood loss, postoperative liver function, surgical complications, and postoperative length of hospital stay were compared between the three groups. Categorical data were analyzed by chi-square test, and continuous data were analyzed using ANOVA followed by Dunnett-t for multiple comparisons. Results There were no significant differences in the operation time and intraoperative blood loss between the three groups ( F = 2. 45 and 0. 34, P > 0. 05 for both) . The recovery of serum total bilirubin ( TBil) and alanine aminotransferase ( ALT) at 1 and 7 d after operation was significantly better in the non-HBFO group ( 1 d, TBil: 22. 4 ± 9. 4 μmol /L, ALT: 287. 4 ± 165. 7 U /L; 7 d, TBil: 17. 1 ± 6. 6 μmol /L, ALT: 86. 2 ± 54. 5 U /L) than in the Pringle group ( 1 d, TBil: 33. 5 ± 11. 9 μmol /L, ALT: 429. 5 ± 137. 8 U /L; 7 d, TBil: 24. 5 ± 7. 0 μmol /L, ALT: 145. 5 ± 43. 6 U /L) and HVC group ( 1d, TBil: 29. 1 ± 8. 3 μmol /L, ALT: 390. 2 ± 176. 6 U /L; 7d, TBil: 21. 5 ± 7. 5 μmol /L, ALT: 121. 5 ± 56. 8 U /L) ( P<0. 05 for all) . The recovery of serum albumin ( Alb) at 1 d after operation was significantly better in the non-HBFO group ( 29. 3 ± 2. 8 g /L) than in the Pringle group ( 27. 3 ± 3. 3 g /L) ( P < 0. 05) , but it showed no significant difference between the non-HBFO group and HVC group ( 29. 3 ± 2. 8 g /L vs 27. 8 ± 2. 5 g /L, P >0. 05) ; there were no significant differences in the recovery of serum Alb at 7 d after operation between the three groups ( P > 0. 05) . The postoperative length of hospital stay was significantly shorter in the non-HBFO group ( 10. 3 ± 2. 1d) than in the Pringle group ( 12. 7 ± 2. 6 d) and HVC group ( 12. 0 ± 2. 2 d) ( P < 0. 05) . Conclusion Compared with Pringle maneuver and HVC, non-HBFO would not increase the intraoperative blood loss and operation time and leads to milder liver function damage and more rapid postoperative recovery in patients with primary liver cancer undergoing hepatectomy.

Values of serum AFP, GGTⅡ and GP73 in diagnosis of primary hepatocellular carcinoma
Zhu Chen, Sun YuanYuan, Jin Yan
2014, 30(10): 1064-1066. DOI: 10.3969/j.issn.1001-5256.2014.10.022
Abstract:

Objective To explore the early diagnostic values of serum alpha-fetoprotein ( AFP) , gamma-glutamyltransferase Ⅱ ( GGTⅡ) , and Golgi protein 73 ( GP73) in patients with primary hepatocellular carcinoma ( PHC) . Methods The serum specimens of 100 patients with liver diseases ( 50 cases of hepatitis and liver cirrhosis and 50 cases of PHC) and 50 healthy people were collected in our hospital from February 2013 to February 2014. Electrochemical luminescence technique, specific immuno-membrane adsorption assay, and enzyme-linked immunosorbent assay were used to measure the serum levels of AFP, GGTⅡ, and GP73. Comparison of continuous data between multiple groups was made by analysis of variance, and comparison between two groups was made by q test. The receiver operating characteristic ( ROC) curves of single or combined test results were made, and the areas under the ROC curves ( AUCs) were calculated. The sensitivity, specificity, and AUCs of AFP, GGTⅡ, GP73, and the combined test were analyzed and compared. Results The level of serum GGTⅡ in the PHC group was significantly different compared with those in the other two groups ( F = 16. 224, P < 0. 05) , but there was no significant difference between the normal group and the hepatitis and liver cirrhosis group ( P > 0. 05) . Significant differences in serum levels of AFP and GP73 were observed by paired comparison between the PHC group, hepatitis and liver cirrhosis group, and normal group ( F =193. 128, F = 20. 231, P < 0. 05 for both) . When assayed alone, the specificities of GP73, GGTⅡ, and AFP were 69%, 64% and 51%, respectively, and the sensitivities were 92%, 84%, and 76%, respectively. In combined test, the specificity was 94. 6% and the sensitivity was 98. 8%. Conclusion The GP73 test is the best performer in the single assays. Combined test of serum AFP, GGTⅡ, and GP73 shows a good diagnostic value for PHC with greatly improved specificity and sensitivity.

Original articles_Others
Clinical efficacy of puerarin combined with compound ammonium glycyrrhetate S in treatment of alcoholic hepatitis
Ji HuiChun, Liu QingDe, Wang HongQi, Li Juan, Zhu Yun, Sun Yang, Zhou ZhongHai, Liu JunQuan
2014, 30(10): 1067-1070. DOI: 10.3969/j.issn.1001-5256.2014.10.023
Abstract:

Objective To investigate the clinical efficacy of puerarin combined with compound ammonium glycyrrhetate S in the treatment of alcoholic hepatitis. Methods A total of 92 patients with alcoholic hepatitis who were admitted to our hospital from February 2011 to February 2014 were recruited in this study and randomly divided into two groups. The control group ( n = 46) was treated with conventional therapy combined with compound ammonium glycyrrhetate S. The test group ( n = 46) was treated with puerarin in addition to the regimen used in the control group. After 20 days of treatment, the levels of total bilirubin ( TBil) , alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , glutamyl transpeptidase ( GGT) , albumin ( Alb) , Glasgow alcoholic hepatitis score ( GAHS) , and abdominal ultrasound were measured and compared with the results before the treatment in both groups. The clinical efficacy and adverse reactions in the two groups were also compared. Results After the treatment, the GAHSs and levels of TBil, ALT, AST, and GGT in the two groups were all significantly lower than those before the treatment ( all P < 0. 05) . In the test group after the treatment, the levels of TBil ( 20. 96 ± 6. 85μmol/L) , ALT ( 33. 72 ±14. 18 U/L) , and AST ( 38. 69 ±6. 38 U/L) were all significantly lower than those in the control group ( all P<0. 05) . The marked response rate, overall response rate, and rate of improvement in abdominal ultrasound in the test group were 63. 04%, 93. 48%, and 44. 44%, respectively, all significantly higher than those in the control group ( all P < 0. 05) . There was no significant difference in adverse reactions between the two groups ( P >0. 05) . Conclusion For patients with alcoholic hepatitis, the combined therapy with puerarin and compound ammonium glycyrrhetate S can improve the treatment outcome and protect the liver function, and it has high safety and holds promise for clinical application.

Anxiety in mice with acute hepatic encephalopathy induced by thioacetamide
Chen QiMing, Yuan Hong, Dai LiRong, Jiang Ni, Ren WenTing, Chen QingFeng
2014, 30(10): 1071-1075. DOI: 10.3969/j.issn.1001-5256.2014.10.024
Abstract:

Objective To evaluate the mental disorders in mice with thioacetamide ( TAA) -induced acute hepatic encephalopathy ( AHE) .Methods Thirty male Kunming mice were equally and randomly divided into two groups ( treatment group and control group) . Mice in the treatment group received an intraperitoneal injection of TAA ( 200 mg·kg-1·d-1for 3 days, up to 600 mg·kg-1) , as compared with the same volume of physiological saline in the control group. Neurological function score, light /dark box, open field, and elevated plus-maze test were used to determine behavioral parameters at 24 h after the model was established. Serum ammonia, aspartate amino transferase ( AST) , alanine aminotransferase ( ALT) , and total bilirubin ( TBil) were measured at 24 h post determination of behavioral parameters. Comparison between two groups was made by independent-samples t test. Results In the light /dark box test, the treatment group had significantly reduced residence time in the light box and number of shuttles between two boxes ( t =-4. 006, P < 0. 01; t =-2. 656, P < 0. 05) ; in the open field test, the treatment group had significantly reduced central distance, central time, and number of vertical movements ( t =-3. 639, P < 0. 05;t =-2. 294, P < 0. 05; t =-2. 282, P < 0. 05) , as well as increased grooming time ( t = 5. 992, P < 0. 01) ; meanwhile, the number of open-arm entries and residence time in the open arm for the treatment group were also reduced in the elevated plus-maze test, as compared with the control group ( t =-3. 584, P < 0. 05; t =-3. 992, P < 0. 05) . However, the total distance in the open field test showed no significant difference between the two groups ( t =-0. 96, P > 0. 05) . Moreover, compared with the control group, the treatment group had significantly higher levels of serum ammonia ( t =-3. 168, P < 0. 05) , ALT ( t = 4. 316, P < 0. 05) , AST ( t =-2. 581, P < 0. 05) , and TBil ( t =-9. 127, P < 0. 01) . Conclusion Mice with AHE induced by an intraperitoneal injection of low-dose TAA have anxiety-related behaviors; the anxiety-related behaviors are not associated with reduced locomotor activities.

Case reports
One case of hepatomegaly due to primary hepatic amyloidosis accompanied by hyperuricemia
Tang ShanHong, Cheng ShuangPing, Qin JianPing, Wu XiaoLing, Chen YiHua, Liang Yan, Ceng WeiZheng, Jiang MingDe
2014, 30(10): 1076-1077. DOI: 10.3969/j.issn.1001-5256.2014.10.025
Abstract:
Reviews
Research progress in prognostic markers of acute-on-chronic liver failure
Zhang YuLing, Han Tao, Zhang Min, Zhang Qian
2014, 30(10): 1078-1081. DOI: 10.3969/j.issn.1001-5256.2014.10.026
Abstract(2543) PDF (1352KB)(1299)
Abstract:
Acute-on-chronic liver failure ( ACLF) is a clinical entity encompassing an acute deterioration of liver function and failure of one or more organs, which results in high short-term mortality rate. In recent years, a number of novel prognostic markers of ACLF have emerged and provided a basis for the treatment and prognostic evaluation of ACLF. Researches on both commonly used and novel makers for prognosis of ACLF are reviewed in order to improve the existing prognostic evaluation system and to provide a basis for the treatment and prognostic evaluation of ACLF.
Analysis of prognostic models for liver failure  
Liu JieYu, Feng YiChao
2014, 30(10): 1082-1086. DOI: 10.3969/j.issn.1001-5256.2014.10.027
Abstract:

Liver failure progresses rapidly, and patients with this disease are usually in a critical condition. The medical treatment of liver failure has unsatisfactory results, leading to a high mortality. How to accurately judge the prognosis of patients with liver failure according to their clinical manifestations and laboratory test results is a very good guide for clinical treatment strategies and donor liver allocation. The prognostic models for liver failure, such as CTP score, MELD and its derivative scoring system, KCH criteria, SOFA score, APACHE scoring system, SMSVH score, Clichy criteria, and ANN, are reviewed. These models are used to guide the development of clinical treatment strategies and screen out patients eligible for liver transplantation. In addition, the prognostic values of these models for liver failure and their differences are evaluated.

Research advances in associations between IL28B polymorphisms and chronic hepatitis B /C virus infection
Shen WenJuan, Ha MingHao
2014, 30(10): 1087-1090. DOI: 10.3969/j.issn.1001-5256.2014.10.028
Abstract:
Chronic infection with hepatitis B/C virus ( HBV/HCV) is a widespread epidemic in China. The single nucleotide polymorphisms ( SNPs) in interleukin 28B ( IL28B) gene have been associated with chronic HBV/HCV infection and response to interferon therapy. The biological functions and characteristics of IL28 B are elaborated on, the associations between HCV infection and IL28 B SNPs are commented on, and current reports of associations between HBV infection and IL28 B SNPs are reviewed. The results support the associations between IL28 B SNPs and disease progression of HCV infection or the curative effect of interferon therapy. However, contradictive results have been obtained in studies of associations between IL28 B SNPs and disease progression of HBV infection, the incidence of liver cirrhosis and primary liver cancer after HBV infection, or the curative effect of interferon therapy, so further investigation is needed.
Research advances in serum biomarkers for early diagnosis of hepatocellular carcinoma
Zhu MingYu, Chen Jie, Zhang XinXin
2014, 30(10): 1091-1093. DOI: 10.3969/j.issn.1001-5256.2014.10.029
Abstract:
Hepatocellular carcinoma ( HCC) is a disease with high incidence and mortality and has become a serious threat to human health.So far, none of the available markers can be used alone for early diagnosis of HCC. Recently identified serum markers with potential clinical value for early diagnosis of HCC are summarized, and their diagnostic sensitivity and specificity, as well as their applications in assessment of progression of the disease, are reviewed. It is suggested that alpha-fetoprotein should be used in combination with other serum markers to achieve accurate diagnosis of HCC at early stages.
Treatment of minimal hepatic encephalopathy
Zhao Kai, Zhang YueXin
2014, 30(10): 1094-1096. DOI: 10.3969/j.issn.1001-5256.2014.10.030
Abstract:
Minimal hepatic encephalopathy ( MHE) is defined as early hepatic encephalopathy without grossly evident neurologic abnormalities, but with cognitive deficits that can be revealed by psychometric testing. However, numerous studies have shown a lack of obvious clinical manifestations in MHE patients, and there is no international unified diagnostic gold standard for this disease. Affected patients' quality of life and ability to work are markedly impaired, and some even gradually progress to symptomatic hepatic encephalopathy. The treatment methods for MHE mainly include eliminating the precipitating factors for this disease and medication. This review presents the options for treatment of MHE and gives an objective evaluation of the efficacy of each treatment scheme. Currently, several treatment methods are used together, but no studies have demonstrated that combined use of treatment methods can improve the treatment outcome.