Abundant experience has been accumulated when it comes to the traditional Chinese medicine(TCM) prevention and treatment of chronic hepatitis B(CHB).However,there still exist some deficiencies such as insufficient randomized controlled trials(RCTs) and lack of attention to objective indices for therapeutic evaluation.Therefore,future clinical prevention and treatment should be tied closely to the research progress in the immune pathogenesis of CHB and give full play to the characteristics and advantages of TCM in modulating the functional status(including immunity) of human body.Moreover,clinical and translational research on the TCM regulation of immune response in CHB should be carried out to further improve clinical therapeutic effect.In addition,biochemistry,virology,and pathology should be applied actively in place of outcomes while paying attention to the symptoms of patients in an effort to improve the objectivity of therapeutic evaluation when summarizing clinical practice experience.Furthermore,RCTs should be employed as much as possible to enhance global recognition of the therapeutic effect of TCM treatment.And there is no doubt that bringing the advantages of integrated traditional Chinese and Western medicine therapy into full play will benefit a huge number of patients.

In recent years,non-invasive methods for assessment of hepatic fibrosis have attracted more and more attention,and the application of non-invasive diagnostic techniques such as serum markers and transient elastography(Fibro Scan) for hepatic fibrosis is reviewed.Anti-fibrosis treatments should integrate etiological treatment,anti-inflammatory and liver-protecting therapy,and inhibiting the synthesis of extracellular matrix and degrading excessively deposited extracellular matrix.Antiviral treatment is the basis for resisting hepatic fibrosis due to chronic viral hepatitis.In this aspect,traditional Chinese medicine(TCM) has advantages in inhibiting the synthesis of extracellular matrix and degrading excessively deposited extracellular matrix,because it effects on multiple links,at multiple levels,and against multiple targets.So integrated traditional Chinese and Western medicine therapy is a promising treatment strategy.However,the benefit of integrative therapy against hepatic fibrosis still needs to be supported by rigorously designed,multicenter,large-sample clinical studies,and the mechanism of anti-fibrosis TCM treatment deserves further studies.

Objective To study the effect of kidney-tonifying and spleen-strengthening prescription(KTSSP) on the expression of programmed death-1(PD-1) and programmed death-ligand 1(PD-L1) in HBe Ag-positive chronic hepatitis B(CHB) patients with slightly increased alanine aminotransferase(ALT) levels.Methods This study included 32 HBe Ag-positive CHB patients with slightly increased ALT levels who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from September1,2010 to December 31,2013.These cases were divided into treatment group and control group using the randomized controlled method.Peripheral blood mononuclear cells were separated,and the expression levels of PD-1 on peripheral blood T lymphocytes and PD-L1 on dendritic cells were measured before and after treatment by flow cytometry.Comparison of continuous data between groups was made by independent-samples t test,while comparison of categorical data between groups was made by chi-square test.Results After treatment,the treatment group had a significantly reduced percentage of peripheral blood CD4+T cells with PD-1 expression(P < 0.01) and a significantly reduced mean fluorescence intensity(MFI) of PD-1 expression on CD4 + T cells(P < 0.05); there were significant differences in the percentage of CD 4+T cells with PD-1 expression and the MFI of PD-1 expression between the treatment group and control group(both P<0.05).After treatment,the treatment group had a significantly reduced percentage of peripheral blood CD8+T cells with PD-1 expression(P < 0.01) and a significantly reduced MFI of PD-1 expression on CD8+T cells(P < 0.01); there were significant differences in the percentage of CD8+T cells with PD-1 expression and the MFI of PD-1 expression between the two groups(both P < 0.05).After treatment,the treatment group had a significantly reduced MFI of PD-L1 expression on dendritic cells(P < 0.05) and myeloid dendritic cells(P < 0.01); there were no significant differences in the expression levels of PD-L1 on dendritic cells and myeloid dendritic cells between the two groups(both P >0.05).Conclusion For HBe Ag-positive CHB patients,KTSSP can reduce the expression levels of PD-1 on peripheral blood CD4+T and CD8+T cells and PD-L1 on dendritic cells and myeloid dendritic cells,which is associated with its clinical efficacy.

Objective To systematically evaluate the efficacy and safety of glycyrrhizin in patients with chronic severe hepatitis B.Methods Literature published from January 1990 to July 2014 were searched in databases including Pub Med,Cochrane Library,CBMdisc,CNKI,VIP,and Wanfang Data.The randomized controlled trials comparing the efficacy of glycyrrhizin combined with internal comprehensive therapy versus internal comprehensive therapy alone in patients with chronic severe hepatitis B were included in the analysis.The methodological quality of included trials was independently assessed and the data were extracted.Meta-analysis was carried out with Review Manager Software 5.1,and the heterogeneity,sensitivity,and bias of the analysis were evaluated.Results Seven randomized controlled trials involving298 patients in the test group and 294 in the control group were included in the analysis.The results of meta-analysis showed that glycyrrhizin combined with internal comprehensive therapy was remarkably more effective than internal comprehensive therapy alone,indicated by significantly reduced mortality rate [relative risk(RR) = 0.56,95% confidenceinterval(CI) :0.42 ~ 0.76,P < 0.01],significantly decreased level of total bilirubin(TBil) [mean difference(MD) =-92.56,95% CI:-122.92 ~-62.20,P < 0.01],and significantly higher prothrombin activity(PTA) [mean difference(MD) = 11.14,95% CI:5.40 ~ 16.87,P < 0.01].No severe adverse reactions were found in all patients.Conclusion Glycyrrhizin can significantly reduce the mortality and improve TBil and PTA in patients with chronic severe hepatitis B.

Objective To systematically evaluate the efficacy of traditional Chinese medicine / herbal decoction combined with ursodeoxycholic acid(UDCA) in the treatment of primary biliary cirrhosis(PBC),and to provide a reference for clinical medication.Methods Literature published before July 31,2014 was searched in databases as follows:Cochrane Library,Pub Med,China National Knowledge Infrastructure(CNKI),Chinese Scientific Journals Full-text Database(VIP),Chinese Biomedical Literature Database(CBM),and Wanfang Data.The randomized controlled trials(RCTs) comparing the efficacy of traditional Chinese medicine / herbal decoction combined with UDCA versus UDCA alone in PBC patients were included in the analysis.The methodological quality of included trials was assessed and the data were extracted,followed by meta-analysis using Rev Man 5.0 software.Results A total of 12 RCTs were included,involving 681 patients with 346 in the test group and 335 in the control group.The results of meta-analysis showed that,after 6 months of treatment,the overall response rate,improvement rate,and biochemical indices of liver function(ALT,ALP,GGT,and TBil) and hepatic fibrosis in the test group were significantly improved compared with those in the control group(all P < 0.05).There were no significant differences between the two groups in the immunological indices such as Ig A,Ig G,anti-mitochondrial antibody(AMA),and AMA M2 subtype(all P > 0.05).Conclusion Traditional Chinese medicine / herbal decoction combined with UDCA markedly improves the indices of hepatocellular necrosis and cholestasis,degree of hepatic fibrosis,and clinical symptoms in PBC patients after 6 months of treatment,but leads to no significant improvement in immunological indices.Due to the limited number of included RCTs and patients through systematic evaluation,and the presence of selection bias and publication bias,more double-blind randomized controlled trials with large sample size,multicenter involvement,and high quality are required to provide convincing evidence.

Objective To investigate the clinical efficacy of Zisheng pills in the treatment of adverse reactions in patients with primary hepatocellular carcinoma(HCC) after transcatheter arterial chemoembolization(TACE).Methods This study included 72 patients with liver cancer hospitalized in the Department of Liver Diseases and Department of Oncology,Wenzhou Hospital of Traditional Chinese Medicine,from June 2011 to May 2014.These cases were randomly divided into treatment group(n = 37) and control group(n = 35).All the patients were treated with TACE,as well as conventional symptomatic and supportive treatment.In addition,the treatment group was given Zisheng pills(one bag) three times a day for at least three consecutive months.Comparison of categorical data was made by chi-square test,while comparison of continuous data(expressed as mean ± SD) was made by t test.Survival comparison was made by Kaplan-Meier method and log-rank test.Results After the first TACE,there were significant differences in poor appetite and abdominal distension between the treatment group and the control group(P < 0.05); significant differences were also observed in CD3+and CD4+T lymphocytes between the two groups(P < 0.05).After the second TACE,there were significant differences in postoperative fatigue,poor appetite,and abdominal distension,as well as postoperative Karnofsky score,between the treatment group and the control group(P < 0.05); significant differences were also found in CD3+,CD4+,and CD8+T lymphocytes and CD4+/ CD8+ratio between the two groups(P < 0.05).The median survival time showed no significant differences between the treatment group and the control group(82 vs 74 weeks,P > 0.05),but the 2-year overall survival rate was significantly higher in the treatment group than in the control group(43.2% vs 20%,P < 0.05).Conclusion Zisheng pills have good clinical efficacy in the treatment of adverse reactions in liver cancer patients after TACE,and it can improve the symptoms and quality of life,regulate peripheral blood T lymphocyte subsets,and increase the 2-year overall survival rate.

Objective To observe the efficacy of Chaowei Zhikangyin in the treatment of the rat model of non-alcoholic fatty liver disease(NAFLD).Methods A rat model of NAFLD was established by feeding 50 Sprague-Dawley rats with high-fat diet for 6 weeks and was confirmed by liver pathological examination.Then,the model rats were randomly divided into five groups:low-,medium-,and high-dose Chaowei Zhikangyin groups(given Chaowei Zhikangyin by gavage),Kezhi capsule treatment group(given a suspension of Kezhi capsules),and model group(orally given distilled water).In addition,control rats were fed with normal diet and then treated with distilled water.Six weeks later,the liver function,blood lipids,liver lipids,and liver histology were examined.Results All Chaowei Zhikangyin groups were superior to the model group in terms of alanine aminotransferase,aspartate aminotransferase,total cholesterol(TC),and triglyceride(TG) in serum and TC and TG in liver tissues(P < 0.05),but there were no significant differences between these Chaowei Zhikangyin groups and Kezhi capsule treatment group(P > 0.05).Different degrees of liver inflammation was observed in the model group and Chaowei Zhikangyin groups; however,the Chaowei Zhikangyin groups and Kezhi capsule treatment group had reduced liver inflammation compared with the model group(P < 0.05),and the Kezhi capsule treatment group showed a significantly more improvement than these Chaowei Zhikangyin groups(P < 0.05).Conclusion Chaowei Zhikangyin can improve liver function,reduce blood lipids,and inhibit liver inflammation in rats with NAFLD,and it has comparable efficacy to Kezhi capsules.This therapy can be used for treating NAFLD.

Objective To investigate the prevalence and major risk factors for fatty liver disease among adult residents in Yan'an,Shanxi Province,China.Methods The study enrolled healthy adults who had physical examination with complete clinical records in our hospital from February 2011 to March 2013.All participants underwent anthropometric measurement(height,weight,and blood pressure),biochemical and immunological tests(liver and renal function; blood glucose,lipids,and uric acid [UA]; viral markers),and ultrasound examination.Data analysis was performed using the t test,χ2test,and logistic regression analysis.Results A total of 6236 adult residents participated in the survey,who accounted for approximately 3.76 /1000 of the total population in Yan'an.There were 3532 males and 2704 females,with a mean age of 49.27 ± 12.93 years.Fatty liver disease was detected with ultrasound examination in 1602 participants(25.68%),among whom alcoholic,suspected alcoholic,and nonalcoholic forms accounted for 4.55%,7.08%,and 88.37%,respectively.The fatty liver group had a significantly higher prevalence of obesity,hypertension,hyperuricemia,higher-than-normal fasting serum glucose(FSG) level,diabetes mellitus,and dyslipidemia than the non-fatty-liver group(P < 0.001).Multiple regression analysis showed that age,gender(male),drinking,waist circumference,body mass index,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglyceride(TG),UA,FSG,diabetes mellitus,and hypertension were influential factors for fatty liver disease,of which HDL-C was a protective factor.Compared with the normal FSG group,the impaired fasting glycaemia and diabetes groups were at an increased risk for fatty liver disease by 1.584-and 2.638-fold,respectively(P < 0.001).The risk increased by1.627-,1.796-,9.544-fold,respectively,in the overweight,grade I obesity,and grade Ⅱobesity groups versus the normal weight group(P< 0.001),by 1.638-and 3.648-fold in the moderate and heavy drinking groups versus the non-drinking group(P < 0.001),and by17.672-fold in the obesity plus drinking group versus the non-obesity or drinking group(P < 0.001).Moreover,the elevated systolic blood pressure,diastolic blood pressure,UA,TG,total cholesterol,and LDL-C groups and the reduced HDL-C group were at a significantly greater risk for fatty liver disease than the normal group,showing 1.835-,1.768-,1.821-,4.524-,1.569-,1.824-,and2.724-fold differences,respectively(P < 0.05).Abnormal TG and HDL-C levels were associated with the most significantly increased risk.Conclusion There is a high prevalence of fatty liver disease(mainly in a nonalcoholic form) among adult residents in Yan'an.Gender,age,obesity,drinking,disorder of glucose metabolism,hyperuricemia,hypertension,and hyperlipidemia are the major risk factors for this disease in the study area.

Objective To investigate the expression and significance of uncoupling protein 2(UCP-2) in rats with obstructive jaundice and bile flow restoration,and to explore the molecular mechanisms of metabolic disorders and oxidative damage caused by obstructive jaundice.Methods Thirty-six healthy male Wistar rats were randomly divided into six groups:sham-operation group(group A),obstructive jaundice for one week(group B),obstructive jaundice for two weeks(group C),obstructive jaundice for one week followed by recanalization for one week(group D),obstructive jaundice for ten days followed by recanalization for one week(group E),and obstructive jaundice for two weeks followed by recanalization for one week(group F).The serum levels of alanine aminotransferase(ALT),direct bilirubin(DBil),and total bilirubin(TBil) were measured.Morphological changes in hepatic tissues were observed under a light microscope.Expression of UCP-2 mRNA in hepatic tissues was assessed by RT-PCR.Results After induction of obstructive jaundice,the serum levels of ALT,DBil,and TBil in groups B and C were significantly elevated compared with those in group A(P < 0.05),and group C had even higher serum levels compared with group B(P < 0.05).Hepatic tissues of group B and C displayed pathological changes,including swelling of hepatocytes,infiltration of inflammatory cells,and bile duct hyperplasia in the portal area.Piecemeal necrosis of liver cells was observed in group C,which was accompanied by more serious pathological changes and increased proliferation of bile ducts and fibrous tissues.Compared with group A,groups B and C showed increased expression of UCP-2 mRNA in hepatic tissues(P < 0.05),and the increase was more prominent in group C(P < 0.05).After restoration of bile flow,the serum levels of ALT,DBil,and TBil in groups D,E and F decreased to varying degrees,and liver morphology tended to be normal.Expression of UCP-2 mRNA in group D was significantly higher than that in group B(P < 0.05),but lower than that in groups E and F(P < 0.05).Group F had significantly lower expression of UCP-2 mRNA than group C(P < 0.05).No significant difference in UCP-2 expression was observed between groups E and F(P > 0.05).Conclusion Expression of UCP-2mRNA in liver is upregulated with the induction of obstructive jaundice,and the level of expression is positively correlated with the duration of obstruction.With early relief of obstruction via bile flow restoration,active regeneration of hepatic tissues occurs,leading to temporary increase in UCP-2 expression.However,with prolonged obstruction,extensive liver damage prevents active regeneration of hepatic tissues,which results in slightly decreased expression of UCP-2.These results indicate that upregulation of UCP-2 may be one of the major mechanisms of metabolic disorders after obstructive jaundice.

Objective To evaluate the diagnostic value of combined determination of DNA ploidy level and microRNA-21(miRNA-21)expression in ascites cells for hepatocellular carcinoma(HCC).Methods A total of 117 patients with ascites admitted to our hospital from January 1,2012 to January 1,2014 were enrolled.The patients with a confirmed diagnosis of HCC were assigned to experimental group(n= 48),and those without HCC to control group(n = 69).The risk factors for HCC were compared between the two groups.Logistic regression analysis was used to extract independent sensitive indicators.The receiver operating characteristic(ROC) curve for each indicator was drawn,and the area under the ROC curve(AUC) and Youden index(YI) were calculated.Results Univariate analysis revealed significant differences between the two groups in sex(male ratio),smoking history,positive rate of HBV,proportion of suspected positive cases based on upper abdominal CT,Karnofsky Performance Scale score,alanine aminotransferase,alpha-fetoprotein(AFP),abnormal prothrombin(APT),α-L-fucosidase,miRNA-21 expression in ascites cells,and the positive rate of DNA aneuploidy in ascites cells(all P < 0.05).Logistic regression analysis showed that smoking history,AFP,APT,miRNA-21 expression in ascites cells,and the positive rate of DNA aneuploidy in ascites cells were sensitive indicators for the diagnosis of HCC.The AUCs of miRNA-21 expression and positive rate of DNA aneuploidy were 0.742 and 0.801,respectively; the AUC and YI of combined use of smoking history,AFP,and APT were0.852 and 0.5992,respectively,while the AUC and YI increased to 0.869 and 0.6222,respectively,if including miRNA-21 expression and positive rate of DNA aneuploidy in combined determination.Conclusion DNA aneuploidy and miRNA-21 in ascites cells are independent risk factors for HCC.The two indicators have good diagnostic values when used separately,and they show increased diagnostic values when used in combination with other parameters(smoking history,AFP,and APT).Combined determination of these indicators has great clinical significance for the early diagnosis of HCC and is a good complement to the current HCC diagnosis system.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE) combined with argon-helium cryoablation in patients with advanced unresectable primary hepatocellular carcinoma(HCC).Methods TACE was performed in 35 patients with primary HCC who were admitted to our hospital from May 2008 to June 2010.After 2-3 weeks of treatment,the patients received argon-helium cryoablation,followed by a second TACE in 1-2 weeks.The short-term efficacy after treatment was evaluated and the long-term survival was studied by follow-up.Comparison between two groups was made by t test,and survival was analyzed using the Kaplan-Meier survival curves.Results The clinical outcomes of all 35 patients were evaluated.Complete response was observed in 7 patients,partial response in 21 patients,stable disease in 4 patients,and progressive disease in 3 patients.The overall response rate was 80.00%,and the disease control rate was 91.43%.The 2-and 3-year survival rates were 45.6% and 39.4%,respectively.The level of alpha-fetoprotein AFP in patients after the treatment(206.2 ± 48.6 μg / L) was significantly lower than that before the treatment(837.6 ±216.7 μg / L)(t = 2.673,P < 0.05).Conclusion TACE combined with argon-helium cryoablation is a reliable therapeutic approach in treating advanced unresectable primary HCC,and the advantages include minimal invasion,fast recovery,and few complications.

Objective To review the multislice computed tomography(MSCT) characteristics and treatment of pyogenic liver abscess in elderly patients.Methods A retrospective analysis was performed on the clinical data of 42 elderly patients who were diagnosed with pyogenic liver abscess in our hospital from March 2001 to February 2014.The MSCT characteristics and clinical treatment of this disease were reviewed.Comparison between two groups was made by t test.Results Among the 42 patients,37 had the liver abscess in the right lobe,and 5 in the left lobe; 33 had single lesions,and 9 had grid-or honeycomb-like lesions.MSCT scan showed that all lesions had a lower density compared with normal hepatic tissues,and the CT values were approximately 6-40 Hu.In the arterial phase,39 patients had lesions with peripheral rim enhancement,and 3 had no edge enhancement.Conservative treatment was given to 15 patients,among whom the diameter of abscess was 3.7 ± 2.1 cm,the duration of fever was 11.7 ± 4.1 d,and the average hospital stay was 22.6 ± 5.3 d.Percutaneous drainage was performed in 27 patients,among whom the diameter of abscess was 6.3 ± 2.8 cm,the duration of fever was 7.1 ± 2.2 d,and the average hospital stay was 13.7 ± 3.1 d.There were significant differences in the diameter of abscess,the duration of fever,and the length of hospital stay between the two groups(P = 0.021,0.026,and 0.006,respectively).Conclusion MSCT can accurately reveal the location and morphology of abscess,and correct diagnosis can be made in combination with the patient's medical history.Drainage guided by ultrasound or CT is an effective,minimally invasive,and safe treatment for controlling fever and promoting fast recovery in the elderly.

Liver failure is a clinical syndrome with severe disorders of liver cells for biosynthesis,detoxication,excretion,and biological transformation,which presents with coagulation disorders,jaundice,hepatic encephalopathy,and ascites.Liver failure progresses rapidly,so the prediction of clinical outcome is significant for the diagnosis and treatment.In recent years,there have been numerous reports on the prediction of clinical outcome in patients with liver failure.The study and application of serological and comprehensive models are reviewed,which provides a reference for the rational therapy for liver failure patients.