Objective To evaluate the efficacies of serum HBsAg levels and HBV DNA loads in prediction of hepatic histological activity grading and fibrosis staging in patients with chronic hepatitis B. Methods 740 patients with CHB were randomly divided into training set and validation set. 281 were HBeAg-positive,and 169 HBeAg-negative in training set,and 170 were HBeAg-positive,and 120 HBeAg-negative in validation set. Liver biopsies were performed,and histological activity grading and fibrosis staging ≥G₂ and ≥S₂,≥G₃ and ≥S₃, and ≥G₄ and ≥S₄ were respectively defined as significant inflammation and significant fibrosis, severe inflammation and severe fibrosis,and advanced inflammation and advanced fibrosis. Serum HBsAg was measured by Abbott Architect I2000,and serum HBV DNA was assayed by real-time PCR. Results In HBeAg-positive patients,the efficiencies of serum HBsAg levels for prediction of severe fibrosis and advanced fibrosis achieved moderate levels in training set,and the areas under ROC curves were 0.707 and 0.726, respectively; the optimal cut-off-value of serum HBsAg levels as determined by Youden indexes for prediction of severe fibrosis and advanced fibrosis were ≤6.683×10³ IU/mL and ≤6.427×10³ IU/mL,and the corresponding sensitivities and specificities in training set were 0.682 and 0.754,and 0.673 and 0.634,respectively,and those in validation set were 0.667 and 0.806,and 0.644 and 0.619,respectively;In HBeAg-negative patients,the efficiencies of serum HBV DNA loads for prediction of significant inflammation and significant fibrosis were significant,and the areas under ROC curves were 0.629 and 0.671,respectively;the optimal cut-off-value of serum HBV DNA levels as determined by Youden indexes for prediction of significant inflammation and significant fibrosis were ≥4.315×10⁴ IU/mL and ≥2.748×10³ IU/mL,respectively,and the corresponding sensitivities and specificities in training set were 0.444 and 0.606,and 0.795 and 0.717,respectively,and those in validation set were 0.446 and 0.613,and 0.797 and 0.622,respectively. Conclusions Serum HBsAg levels in HBeAg-positive patients with CHB have significant values for prediction of severe fibrosis and advanced fibrosis,and serum HBV DNA loads in HBeAg-negative patients have some hints of significant inflammation and significant fibrosis in liver tissues.

Objective To observe the clinical efficacy of combination of entecavir（ETV） and immunotherapy in the treatment of hepatitis B virus carriers. Method 66 hepatitis B virus carriers were randomly assigned into treatment group and control group with 33 in each group. Individuals in the treatment group were treated by ETV and hepatitis B vaccine,rIL-2,and G-CSF,and those in the control group were treated with ETV alone. The regimen lasted for three years in both groups. Before and after the treatment,serum level of ALT,HBV DNA,HBeAg,HBeAb,HBsAg were detected routinely. Results At the end of the treatment,negative rate of serum HBeAg in the treatment group was 33.3%,significantly higher than that in the control group（12.1%,P<0.05）;the seroconversion rate of HBeAg to anti-HBe was 24.2% in the treatment group,significantly higher than that in the controls（6.0%,P<0.05）;the serum HBV DNA loss in treatment group was 75.7%,significant higher than that in the control group（51.5%,P<0.05）;At the end of six months after the discontinuation of the treatment,the negative rate of serum HbeAg was 42.4%,the seroconversion of HbeAg to anti-HBe rate was 27.2%,and the serum HBV DNA loss was 78.7% in the treatment group,all significantly higher than those in the controls（12.1%,6.0% and 45.4%,respectively,P<0.05）;serum levels of ALT were elevated in 42.3% of individuals in treatment group, significantly higher than that in the controls（9.0%,P<0.05）. Conclusion The clinical efficacy of combination therapy with nucleoside analogues and immune-modulating agents are promising,which might break the state of immune tolerance in some hepatitis B virus carriers.

Objective To analyze the Helicobacter pylori（Hp） infection status in Uygur patients with chronic hepatitis B in Xinjiang and helicobacter 16SrRNA gene in liver biopsy tissues. Methods 60 patients with hepatitis B and 80 healthy persons were recruited in this study. ¹⁴C-urea breathing test was used to detected Hp infection,and helicobacter 16SrRNA gene in liver biopsy tissues were detected by using real-time PCR and pathological examination was applied to determine histological activity index. Results The ¹⁴C-UBT positive rate was 85.00% in patients with hepatitis B,significantly higher than 60.24% in the controls （P<0.01）; 14 out of 60 patients with hepatitis B were diagnosed with liver cirrhosis by histopathological examination; the positive rate of helicobacter 16SrRNA in liver tissues from patients with CHB were 86.96%,without significant difference as compared to 92.86% from patients with liver cirrhosis（x²=0.363,P>0.05）;there were no significantly statistical differences as respect to the positive rates of helicobacter 16SrRNA in liver tissues among 21,16 and 9 patients with hepatitis B of mild,moderate and severe degree（x²=1.348,P=0.510）. Conclusion The infection of Hp in patients with CHB is common,but there is no significant evidence showing correlation of the specificity 16SrRNA of Hp to pathological grading and staging in liver tissues.

Objective To investigate the clinical efficacy of interferon alfa-1b combined with entecavir（ETV）in treatment of patients with chronic hepatitis B（CHB） and high serum viral loads. Methods 92 patients with CHB and high serum viral load （HBV DNA≥1×10⁷ IU/ml） were divided into observation group （n=48） and control group（n=44）. Patients in the control group were treated with interferon alfa-1b,and patients in the observation group were treated with interferon alfa-1b combined with ETV. The treatment course in two groups lasted for 48 weeks. The recovery rates of serum alanine aminotransferase（ALT）,rates of serum HBV DNA loss, negative rates of HBeAg and the conversion rates of HBeAg to anti-HBe were compared at 12,24 and 48 weeks. Serum HBV markers and HBV DNA levels were routinely detected. Results The recovery rates of serum ALT at week 24 and 48 in observation group were 68.8% and 91.7%,respectively,significantly higher than those in the control group（34.1% and 63.6%,P<0.01）;The negative rates of serum HBV DNA at week 12,24 and 48 in the observation group were 45.8%,72.9% and 87.5%,respectively,which were significantly higher than those in the control group（11.4%,31.8% and 47.7%,P<0.01）;The negative rate of HBeAg and the conversion rate of serum HBeAg at the end of week 48 in the observation group were 67.6% and 62.2%,significantly higher than those in the control group（42.9% and 37.1%,P<0.05）. Conclusion Efficacy of interferon alfa-1b combined with ETV in treatment of patients with CHB and high serum viral load is superior to IFN alfa-1b monotherapy.

Objective To evaluate the efficacy and safety of tenofovir disoproxil fummte （TDF） monotherapy or in combination with entecavir（ETV） for relapsed chronic hepatitis B patients with nucleos（t）ide resistance. Methods Eleven chronic hepatitis B patients with nucleos（t）ide resistance were treated with TDF. Out of them, six patients were treated with TDF monotherapy and five patients were treated with TDF in combination with ETV. The serum HBV DNA,ALT and serum creatinine（Cr） levels were detected at weeks 4,12,24,36 and 48 since the rescue treatment started. Cumulative probability of serum HBV DNA undetectable rate during the treatment period was calculated by using the Kaplan-Meier method. Results All patients at presentation had nucleos（t）ide resistance mutations,including one patient with ADV-related mutations,seven patients with LAM/ETV-resistant mutations,and three patients with LAM/ETV/ADA-resistant mutations;After rescue therapy,serum HBV DNA level decreased from（4.82± 1.29） lg IU/mL at onset to（3.57± 0.55） lg IU/mL and to （2.91± 0.37） lg IU/mL at 4 and 12 weeks,respectively;At 48 weeks of rescue treatment,serum HBV DNA was detectable in only one of 11 patients;Serum HBV DNA became undetectable in 36.4%（4/11）,63.6%（7/11）,81.8%（9/11） and 90.9% （10/11） of patients at 4,12,24 and 36 weeks of rescue treatment, respectively;Serum ALT levels decreased from（64.36± 34.55） U/L at onset to（37.7± 24.49） U/L at the end of follow-up;There were no renal dysfunction or other adverse events observed during treatment. Conclusion TDF monotherapy or in combination with ETV is effective in reducing serum HBV DNA levels and is safe for CHB patients with nucleos（t）ide resistance.

Objective To illuminate the relationship between natural progressive course of chronic hepatitis B virus infection and the factors such as the time of infection,serum HBV DNA load,HBeAg status,and thickness of spleen. Method 132 patients with chronic hepatitis B infected with family cluster were enrolled in Shengjing hospital affiliated to China Medical University from January 2007 to August 2010. Liver biopsy,serum HBV markers and HBV DNA were routinely obtained. Results The prevalence of hepatic inflammation score≥5 and fibrosis score≥3 were 33.3% and 38.4% in patients aged >30 years old,significantly higher than 14.9% and 14.8% in age ≤30 years group（P<0.05）;The prevalence of inflammation score≤4 and fibrosis score ≤2 were 92.0% and 92.0% in individuals with normal liver function group, significantly higher than 53.6% and 16.74% in with abnormal liver function group（P<0.05）; The prevalence of inflammation score≤4 and fibrosis score ≤2 were 100.0% and 83.3% in patients with serum HBV DNA load <3 lg copies/ml,much higher than in patients with serum HBV DNA load >3 lg copies/ml;There was no statistical difference in hepatic inflammation score between patients with serum HBeAg-negative and HBeAg-postive group;The patients with spleen thickness≥4 cm had higher hepatic inflammation and fibrosis score than in with spleen thickness<4 cm（P<0.05）;In multivariate analysis,the spleen thickness（P=0.033） and serum HBV DNA（P<0.01） had independent positive correlation to liver inflammation and fibrosis. Conclusion The time of infection has positive correlation to the severity of liver inflammation and fibrosis in patients with chronic hepatitis B virus infection with family cluster. It shows up the progress of liver disease go ahead when age is greater than 30 years old;The abnormal liver function continues,the more serious liver inflammation and fibrosis stands;Spleen thickness has independent positive correlation to liver inflammation and fibrosis;It is more serious in liver inflammation and fibrosis when serum HBV DNA load are in the range of 1×10³~10⁵ copies/ml;Serum HBeAg-negative chronic hepatitis B patients with a family cluster may have more serious liver fibrosis than in serum HBeAg-positive ones.

Objective To analyze the characteristics of tongue and pulse parameters in patients with chronic hepatitis B （CHB）,and to provide evidence for the clinical syndrome differentiation of Traditional Chinese Medicine（TCM） in patients with CHB. Method Tongue and pulse parameters of 120 patients with CHB and 45 health persons were detected and analyzed by DS01-A type digital tongue and pulse presentation analyzer. Results Compared with those in the healthy controls,the pulse parameters of h3/h1,h4/h1,W/t in patients with CHB increased,while h5/h1 decreased, and the difference was statistically significant （P<0.05）;the h3/h1 and h4/h1 of patients in damp heat group were higher than those of patients with yin deficiency of liver and kidney group（P<0.05）,but h3/h1 in patients of liver stagnation and spleen deficiency group was higher than that of patients with yin deficiency of liver and kidney（P<0.05）;Compared with the healthy control group,tongue parameters including R,G,B,V values in patients with CHB decreased and S value increased,and the difference was statistically significant（P<0.05）;Compared with the blood stasis group,the R values of patients with damp heat with liver stagnation and spleen deficiency or yin deficiency of liver and kidney increased（P<0.05）,but B values decreased（P<0.05）;The S values of patients with damp heat with liver stagnation and spleen deficiency were lower than that of patients with blood stasis（P<0.05）;The B value of patients with yin deficiency of liver and kidney was higher than that of patients with damp heat（P<0.05）. Conclusion Detection of the tongue and pulse parameters can reflect the change of liver functions in patients with CHB,and provide evidence for the clinical syndrome differentiation of TCM.

Objective To evaluate the diagnostic value of FibroTouch^® by fat attenuation index（FAI） in patients with non-alcoholic fatty liver diseases（NAFLD）. Methods A total of 86 patients with NAFLD and 90 healthy persons were recruited in this study. NAFLD group was divided into mild,moderate and severe liver steatosis based on B-ultrasonography. Two independent sample t-test was used to compare body mass index （BMI）,FAI and liver stiffness were obtained by FibroTouch^® between NAFLD group and healthy control. One-way analysis of variance was used to compare above parameters among mild,moderate and severe liver steatosis. Pearson correlation was used to analyze the relationship between FAI and BMI or liver stiffness. Receiver operating characteristic（ROC） curves were plotted,and the areas under the curves（AUC） were calculated. The cut-off values were defined by maximizing the sum of sensitivity and specificity（maximum Youden index）. Results Between control group and NAFLD group,BMI were [（22.9±2.1） kg/m² and （27.8±3.4） kg/m²,P<0.001],FAI were [（215.1±16.3） db/m and （263.0±25.1） db/m,P<0.001],liver stiffness were [（5.1±1.1） Kpa and （8.8±5.7） Kpa,P<0.001];Among mild（n=43）,moderate（n=28）,severe（n=15） liver steatosis,FAI showed significant difference [（244.0±9.9） db/m,（273.8±9.7） db/m and（301.9±20.1） db/m,P<0.001];FAI showed positive correlation with BMI （r=0.741,P<0.001） and liver stiffness （r=0.442,P<0.001）;AUC of normal vs. mild,mild vs. moderate, and moderate vs. severe were（0.935,0.986,and 0.969,respectively,P<0.001）;The cut-off values for mild, moderate,and severe liver steatosis were 237 db/m（sensitivity 96.7%, specificity 86.4%）,259 db/m （se. 97.7%, sp. 92.9%）,and 286 db/m（ se. 96.4%,sp. 93.3%）,respectively. Conclusion FAI shows advantages in diagnosing NAFLD,and has a promising diagnostic potential for grading liver steatosis in patients with NAFLD.

Objective To investigate the prevalence of anemia in patients with hepatitis B virus-induced acute-on-chronic liver failure（ACLF）,and to evaluate its association with short-term survivals. Methods Hospitalized patients with HBV related acute-on-chronic liver failure,cirrhosis or chronic hepatitis B were recruited from December 2011 to January 2013 in this study. The peripheral blood index were routinely assayed. The prevalence and progression of anemia and clinical outcome of patients were observed. Results There were 171 patients included in this study. 2.5% out of 40 patients with chronic hepatitis B,34.7% out of 49 patients with liver cirrhosis and 45.1% out of 72 patients with ACLF had anemia at admission;and the percentages of mild,moderate and severe anemia in patients with ACLF were 26.8%,17.1% and 1.2%,respectively;Anemia in patients with ACLF exacerbated within first hospitalization week（122.4g/L vs. 112.7g/L,P=0.001）;the blood hemoglobin levels in survived patients with ACLF（n=42） increased（112.7 g/L vs. 147.5 g/L,P=0.001）;Blood hemoglobin levels in patients with ACLF at admission（cut-off value was 125.5 g/L） was an predictor for 90-day survivals （AUROC=0.735,P<0.001）. Conclusions Anemia in patients with ACLF is common and severe,which might aggravate within one week and recover in survivals.

Objective To investigate the distribution characteristics of hepatitis B virus genotypes in patients with CHB or hepatitis B cirrhosis,and to explore the mutants patterns in HBV P gene sequences during nucleos（t）ide analogue（NAs） treatment. Methods 39 patients with CHB or hepatitis B cirrhosis observed drug resistance or suspected drug resistance were enrolled. Serum HBV DNA levels was detected by real time PCR, and then sequenced and compared with standard sequence in HBVseq datebase. Results The genotypes of HBV in 34（87.2%） patients were observed,and the genotype C was found in 32（82.1%）,and genotype B in 2 （5.1%）. 27（69.2%） of 39 patients were observed carrying mutation in RT gene sequence;point mutations accounted for 30.8%,including 6 harboring rtM204I/V/（15.4%）,2 harboring rtA181V/T（5.1%）,and 4 harboring rtI169T （10.3%）,and combination mutations were 38.4%;there were 23 patients detected to be resistant to NAs. 8 patients were resistant to adefovir dipivoxil（ADV）,and among them,one was genotype B,and the other 7 were genotype C,harboring rtA181V/T/S,rtV214A/E or rtN236T;11 patients were resistant to both lamivudine（LAM） and telbivudine （LDT） with genotype C,harboring rtM204I/V/S or rtL180M;3 patients were resistant to LAM,LDT and entecavir（ETV）,and they were all with genotype C;1 patient with type C was resistant to LAM, LDT and ADV, and the mutation pattern was rtM204I/V/S+rtA181V/T/S+rtL180M. Conclusion HBV P mutations exist in most patients with chronic hepatitis B;the rtM204I/V/S mutations is the dominate mutation pattern,and different NAs may share the common mutations.

Objective To observe the effects of goat milk powder diet on nutrition condition and synthetic function of liver in patients with hepatitis B-induced liver cirrhosis. Methods Eighty patients with hepatitis B-related liver cirrhosis were enrolled in this study,and 40 cases were treated with goat milk powder in treatment group and 40 cases were treated with regular dieteric were treatment in control group. Evaluation of nutrition condition and liver function tests were conducted for 12 weeks in both groups. Analyses were carried out by using t test. Results At 4 week and 8 week observation,there was no significant difference of nutrition indicators and liver synthetic funtion,including body mass index,arm muscle circumference,serum albumin,pre-albumim,transferrin and cholinesterase levels between the two groups;the body mass index [（23.36±1.26） kg/m² vs. （22.30±1.80） kg/m², t=3.021,P<0.05],arm muscle circumstance[（27.89±2.85） cm vs.（26.16±3.04） cm,t=2.766,P<0.05],albulmin [（34.93±1.63） g/L vs.（32.04±1.80） g/L,t=7.597,P<0.05],pre-albulmin [（91.97±21.14） mg/L vs. （76.92±15.94）mg/L,t=3.415,P<0.05],transferrin [（1.69±0.35） mg/L vs.（1.50±0.34） mg/L,t=2.315,P<0.05] and cholinesterase[（2785±516）U/L vs.（2546±487） U/L,t=2.105,P<0.05] in the treatment group at week 12 were significantly increased as compared to those in the control group,while the serum levels of total bilirubin,blood ammonia, plasma triglyceride and blood sugar showed no significant differences between the two groups. Conclusions Dietary intervention with goat milk powder can improve nutrition condition and liver synthetic function in patients with hepatitis B-induced liver cirrhosis.

Objective To investigate the hospitalization costs of patients with alcoholic liver cirrhosis and explore the factors influencing the hospitalization costs. Methods A total of 1907 inpatients with alcoholic liver cirrhosis from 2011 to 2013 were included in this study. Multiple linear regression were applied to analyze the hospitalization costs and the relevant factors. Results The number of hospitalized patients with alcoholic liver cirrhosis showed an increasing trend and hospitalized patients were 476,577 and 855 in 2011,2012 and 2013; there were 1879 males and 28 females,with a average age of （51.60±8.70） years old,and 77.77% were 40 to 60 years old;the average hospital stay were （19.78±15.58） days,and the average cost were（27900.32±26580.54）Yuan,among which the costs of western medicine,laboratory test and examining materials accounted for 65.01%,12.43% and 8.11%,respectively;The main factors affecting the hospitalization costs were time of hospitalization stay,albumin transfusion,blood transfusion,discharged year and marital status. Conclusion The hospitalization cost of patients with alcoholic liver cirrhosis are relatively high,and efforts of patients,families,hospital and society are all needed to control the hospitalization cost.

Objective To explore the imaging manifestation of portal collateral vessels by CT angiography in patients with liver cirrhosis. Methods A retrospective study were carried out in 216 patients with cirrhotic portal hypertension,who were treated in our hospital from January 2013 to January 2014. The clinical data,CT portal angiography and three dimensional reconstruction image of portal collateral vessels in all patients were analyzed. Results The distribution,pathway and anatomy of portosystemic collateral vessels were well shown by CT portal angiography in all 216 patients;Among them,there were 172（79.63%） patients with left gastric varices,100（46.30%） with lower esophageal varices,51 cases（23.61%） with paraesophageal varices,50 cases （23.15%） with gastro-renal shunt and/or splenorenal shunt,and 36 cases （16.67%） with paraumbilical varices and varicosity of abdominal wall;There existed significant difference in the diameter of portal vein and splenic vein between patients with gastro-renal shunt and/or splenorenal shunt [（12.64±1.12） mm and（18.72±3.48） mm,respectively] and patients without shunt [（19.56±5.64）mm and（13.47±2.35）mm,respectively,P<0.05]. Conclusion CT portal angiography can clearly show the distribution and severity of collateral vessel in patients with cirrhotic portal hypertension,which can help accurate diagnosis.

Objective To investigate the application of computed tomography（CT） and magnetic resonance imaging （MRI） in diagnosis of agenesis of right hepatic lobe. Method Twenty-four patients with agenesis of right hepatic lobe were recruited in our hospital,and they were all checked-up by CT and MRI. Results Our series included eight men,and sixteen women,with the average age of（60.7±3.2） yr-old;the agenesis of right hepatic lobe were diagnosed by MRI in 6,by CT in 18,and by both in 4;the imaging showed shrunk volume of right lobe,narrow portal vein and even lost its branches;left hepatic lobe enlarged in 18,and with normal left hepatic lobe in 6;hepatic caudate lobe shrank in 3,and enlarged in 15;extrahepatic bile duct stone in 14,dislocation of gall bladder in 12;all patients had cholangiectasis,12 had splenomegaly,and 9 had neoplasm. Conclusion The application of CT and MR imaging for the diagnosis of right lobe dysplasia have important clinical significance.

Recently,transient elastography is widely used in diagnosis of patients with chronic liver diseases. Scholars worldwide have found that the technology would be helpful for noninvasive diagnosis of liver fibrosis, monitoring effect of treatment and predicting prognosis of liver disease. This review will focus on the principle,application and impact factors in this technology.

Similar pathologic characteristics between non–alcoholic fatty liver disease and alcoholic liver disease presents a new direction for the hepatologists worldwide that endogenous alcohol may play important role in the development of non–alcoholic fatty liver disease. The closed relationship among endogenous alcohol and liver,intestine,intestinal flora and non–alcoholic fatty liver disease provides a new sight to explain the pathogenesis of non–alcoholic fatty liver diseases.

Incidence of hepatocellular carcinoma（HCC） is increasing worldwide. The development of HCC tends to be related to hepatitis virus infection. However,nonalcoholic fatty liver disease is another important cause of hepatocellular carcinoma. In recent years,with the change of lifestyle and diet habits,the incidence of nonalcoholic fatty liver disease is increasing,and more and more studies have focus on the relationship between nonalcoholic fatty liver disease and hepatocellular carcinoma. The process,risk factors and mechanism of nonalcoholic fatty liver disease–related hepatocellular carcinoma will be reviewed in this paper.

The cornerstone of therapy for alcoholic hepatitis are abstinence and nutritional support. Many therapeutic interventions have been studied in alcoholic hepatitis but have been unable to show convincing benefit. These interventions included, Corticosteroids,Pentoxifylline,N-acetylcysteine,inhibitors of TNF-α,etc. High quality clinical trials research is essential in China. Liver transplantation（LT） confers a survival benefit in patients with ALD. However,alcohol relapse after transplantation remains a critical issue and drinking habits of transplanted patients need to be routinely screened.

Liver fibrosis is a pathological process characterized by intrahepatic diffuse excess deposition of extracellular matrix （ECM）,which is also a common response occurred in the progression of varied chronic liver disease to cirrhosis. As ECM is mainly secreted by hepatic stellate cells（HSC） and its activation process is the central part of liver fibrosis development. In this review,we will summarize the mechanism of HSC activation in combination with the roles of hepatocytes,other non-parenchymal cells and various profibrogenic cytokines. This paper will also describe the significance of intestinal flora alteration and aberrant expression of microRNAs in the development of liver fibrosis.

Liver fibrosis is an inevitable process of chronic liver diseases with different causes which might lead to end-stage liver diseases. In recent years, the serologic diagnosis of liver fibrosis gets widely attention for its non-invasiveness and good repeatability. The serologic diagnosis of liver fibrosis includes conventional serologic markers,serologic diagnostic models, omics,genetics,and the joint application of two or more methods.