Objective To investigate the clinical effect of magnesium isoglycyrrhizinate combined with reduced glutathione in the treatment of patients with chemotherapeutic drug-induced liver injury. Methods 80 patients with chemotherapeutics-induced liver injury were randomly divided into two groups. Patients in combination treatment group（n=45） were treated intravenously with magnesium isoglycyrrhizinate combined with reduced glutathione for 2 weeks,and the patients in control group（n=35） were treated with reduced glutathione alone. The serum levels of ALT and AST were observed. Results At the end of 2 week treatment,the serum levels of ALT and AST in control group were（88±45） U/L and（98±53） U/L,significantly decreased as compared with those pre-treatment [（130±60） U/L,and （138±70） U/L,P<0.05];serum levels of ALT and AST in combination treatment group were（55±38） U/L and（56±43） U/L,significantly decreased as compared with those pre-treatment [（125±47） U/L,and （158±68） U/L,P<0.05] in this group and in the controls （P<0.05）;In patients aged younger than 60 years,the serum levels of ALT and AST in 27 patients receiving combination treatment after treatment were （45±23） U/L and（40±35） U/L,and those in 20 patients in control decreased to （60±30） U/L and（65±34） U/L];while in patients older than 60 years,the serum levels of ALT[（103±45） U/L] and AST [（99±50）U/L] after combination treatment in 18 patients were significantly lower than those in 15 controls[（145±80） U/L and（151±65） U/L,P<0.05]. Conclusion Magnesium isoglycyrrhizinate combined with reduced glutathione is effective in the treatment of patients with chemotherapeutic drug-induced liver injury.

Objective To investigate the changes of peripheral blood CD3⁺CD4^-CD8^-T cells （double negative T,DNT） and T lymphocyte subsets in patients with hepatitis B virus（HBV） infection. Methods The peripheral blood DNT cells and T lymphocyte subsets were detected by flow cytometry in 136 HBV cases including asymptomatic carriers（ASCs,n=33）,acute hepatitis B（AHB,n=28）,mild chronic hepatitis B（n=28）, moderate chronic hepatitis B（n=25）,severe chronic hepatitis B（n=22） and healthy persons（n=39）. Results The percentages of DNT cells in healthy persons and in patients with AHB were（4.82±3.43）% and（4.75±2.71）%,respectively,both of which were significantly lower than that in ASCs[（5.43±3.31）%,P<0.05];The percentage of DNT cells in patients with mild CHB was（7.97±4.12）%, significantly lower than in patients with severe CHB[（11.36±5.01）%,P<0.05],and the percentage of DNT cells in patients with moderate CHB was（8.41±4.93）%,also significantly lower than in patients with severe CHB（P<0.05）;There were no differences in percentages of T lymphocyte subsets among health persons,patients with acute hepatitis B and ASCs;The percentages of CD3⁺ and CD3⁺CD4⁺CD8^- cells decreased（P<0.05） and the percentage of CD3⁺CD4^-CD8⁺ cells increased （P<0.05） in patients with chronic severe hepatitis B. Conclusions The increase in peripheral blood DNT cells is associated with the chronicity of illness in patients with CHB.

Objective To investigate the efficacy of combination therapy of interferon-α（IFN-α） plus entecavir（ETV） or IFN-α monotherapy in the treatment of patients with chronic hepatitis B（CHB）. MethodsArticles published before February 10,2013 in database of PubMed,EMbase,Cochrane Library,China Biology Medicine disc,CNKI and WANFANG were searched. All eligible randomized controlled trials were included. Review Manager. 5.1.0 for Windows was used for Meta-analysis. Results Four articles that met the inclusion criteria were obtained,including a total of 259 patients with chronic hepatitis B,of which 115 received combination therapy and 144 received interferon-α alone. The funnel plot analysis showed that the research was distributed symmetrically with the true value as the center. HBV DNA negative rate in patients in combination therapy was higher than patients receiving monotherapy at 24 w and 48 w,and the differences were statistically significant[78.3%（90/115） vs. 42.4%（61/144）,RR=1.89,95% CI 1.52~2.36,P<0.00001,and 92.6%（88/95）vs. 63.7%（79/124）,RR=1.46,95% CI 1.26~1.70,P<0.00001];serum HBeAg conversion rate in patients in combination therapy group was significantly higher than patients receiving monotherapy at 24 w and 48 w[37.4%（43/115）vs. 27.1%（39/144）,RR=1.46,95% CI 1.03~2.08,P=0.03,and 64.2%（61/95）vs. 39.5%（49/124）,RR=1.55,95% CI 1.19~2.01,P=0.001];ALT normalization rate in patients receiving combination therapy was also significantly higher than in patients with monotherapy at 24 w and 48 w [75.7%（87/115）vs. 45.8%（66/144）,RR=1.71,95% CI 1.39~2.11,P<0.00001,and 93.7%（89/95）vs. 66.1%（82/124）,RR=1.41,95% CI 1.23~1.61,P<0.00001]. Conclusions Efficacy of interferon-α plus entecavir in the treatment of patients with CHB is superior to IFN-α monotherapy.

Objective To investigate the efficacy and safety of adefovir dipivoxil combined with oxymatrine in the treatment of patients with HBeAg-positive chronic hepatitis B（CHB）. Methods Eighty patients with HBeAg-positive CHB were randomly divided into control group（n=40） and treatment group（n=40）. Patients in control group were treated with ADV,while patients in treatment group were treated with ADV combined with oxymatrine. All patients were treated for 12 months. At 3,6,9 and 12 month,symptoms and signs, serum biochemical parameters,serum HBV DNA levels,serological HBV markers and adverse events were observed. Results At 6,9 and 12 month,serum HBV DNA levels in treatment group were（3.97±1.15）lg copies/ml,（3.38±1.24） lg copies/ml and（3.09±1.19） lg copies/ml,significantly lower than in the controls[（4.61±1.32） lg copies/ml, （4.17±1.12） lg copies/ml and （3.81±1.26） lg copies/ml,respectively,P<0.05];serum alanine aminotransferase （ALT） levels at 3,6 and 9 m were similar between the two groups and were lower than in the pre-treatment levels; serum ALT levels in patients of treatment group at 12 m was（30.1±15.4） U/L,significantly lower than in the controls [（39.9±14.5）U/L,P<0.05];serum HBV DNA loss at 3 m and normalization rates of ALT level at 3 m and 6 m did not differ between the two groups,but the rates of HBV DNA loss in patients in treatment group at 6,9 and 12 m were 55.0%,65.0% and 77.5%,respectively,significantly higher than in the controls[32.5%,42.5% and 57.5%,respectively,P<0.05];normalization rates of ALT level of patients in treatment group at 9 and 12 m were 82.5% and 92.5%,significantly higher than in the controls[60.0% and 75.0%,respectively,P<0.05];negative rates and seroconversion rates of HBeAg for patients in treatment group at 12 m were 47.5% and 42.5%,respectively,significantly higher than in the controls[25.0% and 20.0%,respectively,P<0.05]. Serious adverse reactions did not occur during the treatment process in the two groups. ConclusionsADV combined with oxymatrine in treatment of patients with HBeAg-positive CHB is of good efficacy and safe.

Objective To summarize the clinical characteristics of patients with human parvovirus B19（HPV） infection. Methods The clinical materials in 17 patients with human parvovirus B19 infection was retrospectively summarized,and the clinical features,laboratory findings and radiologic imaging were analyzed. ResultsThe predominant symptoms and signs of patients in this series were:fever（100.0%）,general fatigue （82.4%）,arthralgia/myalgia （52.9%）,pharyngalgia（17.4%）,anorexia（64.7%）,rash（17.3%）,splenomegaly （70.6%）, hepatomegaly （41.2%）,lymphadenectasis （17.6%） and jaundice （17.3%）;The laboratory findings showed elevated serum alanine aminotransferase and aspartate transferase,lactate dehydrogenase,hydroxybutyrate dehydrogenase and adenosine deaminase levels,and higher lymphocyte counts;Hepatic injury caused by HPV B19 infection had features of acute onset and complicated clinical manifestations, but with a self-limited illness course. The recovery of liver function was rapid and the prognosis was relatively good. ConclusionThe patients who have unexplained hepatic injury should have a prompt detection of serum anti-HPV B19 IgM,especially in those with negative serum hepatitis A,B,C and E virus markers.

Objective To investigate the etiologies and the pathological characteristics of patients underwent liver biopsy. Methods 1571 patients underwent liver biopsies were collected from 2007 to 2013 and they were all excluded from neoplastic diseases. Results The 5 common causes of nonneoplastic lesions in our series were unknown etiology （73.6%）,hepatitis B （10.0%）,fatty liver （7.4%）,primary biliary cirrhosis （4.1%） and hepatitis C（1.6%）;Patients with unknown etiology were usually accompanied by other visceral damage which resulting in nonspecific hepatic lesion;the main clinical symptoms of hepatitis B were fatigue,loss of appetite and jaundice,and its pathological characteristics included ground glass hepatocytes,cellular swelling and spotty and focal necrosis;The hepatic steatosis was diagnosed based on relevant risk factors and the exclusion of other etiologies;Primary biliary cirrhosis was featured by serum anti-mitochondria antibody positive and chronic nonsuppurative damage of small bile ducts;Patients infected with hepatitis C might be asymptomatic,and the pathological characteristics included hepatocellular swelling,hepatic steatosis,fibrous hyperplasia and lymphocytic infiltration in portal area. Conclusion With their respective pathological characteristics,liver diseases of unknown etiology,hepatitis B,fatty liver disease,primary biliary cirrhosis and hepatitis C are the main diagnosis by liver biopsies.

Objective To investigate the clinical features in patients with cryptogenic hepatitis and establish a standardized road-map for diagnosis of them. Methods Patients with elevated serum alanine aminotransferase （ALT） levels from 2010 to 2013 were included in this study. Patients passed through screening,detailed examination,and follow-up stages as necessary. History-taking,physical examination,radiography,blood tests including highly sensitive detection of virus nucleic acid and gene locus testing,liver histopathology and immunohistochemistry and diagnostic scoring system were applied to find out the etiology. Results A total of 143 patients（14.3%） with cryptogenic hepatitis were left from 1000 individuals with elevated serum ALT levels;After detailed examination and/or follow-up for months,21 patients got diagnosis including three with hepatitis B,four with viral hepatitis,thirteen with autoimmune liver diseases,and one with drug-induced liver injury,while the causes in other 122 cases（12.2%） were still unknown;Serum ALT and TBIL levels in the 122 patients with cryptogenic hepatitis were （640.01±596.67） IU/L and （118.41±142.64） μmol/L;Out of the 122 patients,53.3%（65/122） had fatigue,71.3%（87/122） had gastrointestinal symptoms,and 50.0%（61/122）had jaundice;The liver histopathologic exam showed that 87.5% （70/80） got mild to moderate histological activity index and 72.1%（88/122）patients got good prognosis. Conclusions At present,about 10% of patients with elevated serum ALT levels are cryptogenic,although the detailed screening processes and very highly sensitive tests can be applied for the clinical practice.

Objective To systematically review the efficacy of entecavir （ETV） and lamivudine （LAM） for the treatment of patients with hepatitis B virus（HBV）-related liver failure. Methods We searched PUBMED, MEDLINE,EMBASE,CNKI,VIP,Chinese Biomedical Literature Database（CBM） and Wanfang database for randomized controlled trials（RCT） comparing entecavir and lamivudine in the treatment of severe hepatitis B or HBV-related liver failure up to April 1,2014. According to the inclusion and exclusion criteria, screening of RCT articles,data extraction and quality assessment were completed by two invastigators independently. The meta-analysis was performed by using the RevMan 5.2 software. Results Fourteen studies involving 1383 patients were enrolled（622 cases in ETV group and 761 in LAM group）. The results of meta-analysis showed that at 12 w and 24 w,ETV was more effective in reducing serum ALT and total bilirubin levels than LAM and the differences were statistically significant（z=3.24 and z=2.26,P<0.02;z=1.92 and =2.23,P<0.03）;ETV significantly elevated PTA levels than LAM at 12 w （z=2.09,P=0.04）,but not at 24 w （z=1.76,P=0.08）;At 12 w and 24 w,there were no statistical differences between ETV and LAM in HBeAg seroconversion （18.2% vs. 13.6%,P=0.68;or 49.5% vs. 52.1%,P=0.93）;At 12 w and 24 w,HBV DNA loss were 37.5% and 77.5% in ETV group, significantly higher than those in LAM group（23.0% and 52.0%,respectively,P<0.05）;The mortalities in ETV group were 8.2% and 12.8% at 12 w and 24 w,significantly lower than in LAM group（18.6% and 19.6%, respectively,P=0.05）. ConclusionsEntecavir is more effective in improving liver function,inhibiting viral replication and reducing mortality in patients with HBV-related liver failure when compared with LAM.

Objective To observe the efficacy and nursing care of combined continuous veno-venous hemofiltration and bilirubin adsorption therapy in patients with hepatic failure. MethodsThe effectiveness, treatment duration,complication incidence,treatment costs and nursing workload were compared between 32 patients treated with combined continuous veno-venous hemofiltration and bilirubin adsorption therapy and 44 patients treated with sequential plasma adsorption and continuous renal replacement treatment. Results On the 7th day of treatment,the efficacy of combined continuous veno-venous hemofiltration and bilirubin adsorption therapy were superior to that of sequential plasma adsorption and continuous renal replacement treatment [total bilirubin （161.1±45.1）vs.（218.9±58.5） μmol/L,bile acid（130.5±60.5） vs. （198.6±49.6） μmol/L,aspartate aminotransferase （152.4±96.3） vs. （252.4±169.1） IU/L,alanine transaminase （147.2±72.6） vs.（220.1±110.3） IU/L,international normalized ratio （1.6±0.4） vs. （1.6±0.4）,preparing time （1.0±0.1） vs. （1.3±0.1） h,treatment duration （7.2±0.5） vs. （11.1±0.7） h and treatment costs（11.0±1.0） vs.（13±1.0） grand RMB,P<0.05 for all]. Complication incidence in both groups showed no difference. ConclusionCombined continuous veno-venous hemofiltration and bilirubin adsorption therapy has preferable efficacy in treatment of patients with liver failure,and effectively reduces the nursing workload and treatment costs.

Objective To observe the influence of 4-week mimic metabolic endotoxemia on hepatic histology and Toll-like receptor 4（TLR4） signaling pathway in mice. Methods Thirty male C57BL/6J mice were randomly divided into normal （n=10） and endotoxin（n=10） groups,fed with normal diet,and high-fat（n=10） group,fed with high-fat diet. The mice in endotoxin group were implanted with subcutaneous osmotic minipump to infuse endotoxin at 300 μg·kg^-1·d^-1 for 4 weeks. The mice in normal group were implanted with minipump filled with saline as control. At the end of the 4th week,the serum endotoxin level were detected. NAFLD activity score（NAS） of liver tissue was evaluated. The mRNA levels of hepatic TLR4,MyD88 and TRAM were detected by real time PCR. Results Serum endotoxin level in endotoxin group[（0.62±0.04） EU/ml] was significantly higher than that in normal group [（0.50±0.06） EU/ml,P<0.05] and in high-fat group [（0.49±0.05） EU/ml,P<0.05]; The dominant histology change of liver in endotoxin mice was simple steatosis and the NAS score was（2.30±0.49）,while the mice in high-fat group had more severe hepatic inflammation and the NAS score was（4.20±1.61）,which was significantly higher than that in the endotoxin group（P<0.05）;The TLR4 mRNA level in endotoxin group was 5.12 times higher（P<0.01） and TRAM mRNA level was 3.46 times higher（P<0.01） as compared with in normal group, but the MyD88 mRNA levels in the three groups had no significant difference. Conclusion Four-week mimic metabolic endotoxemia induces hepatic steatosis with increased levels of hepatic TLR4 and TRAM mRNA,but has no effect on the hepatic MyD88 mRNA.

Objective To establish an animal model of early primary biliary cirrhosis （PBC） by injection of polyinosinic-polycytidylic acid（Poly I:C）. Methods Thirty female C57BL/6 mice were randomly divided into model and control group. Mice in model group were injected with poly I:C at a dose of 5 mg.kg^-1 while animals in control with equal volume of saline for 24 weeks. The antimitochondrial antibody-M2（AMA-M2）,CD4⁺CD25⁺Foxp³⁺ cells were detected at 8,16 and 24 weeks. Histological changes of liver samples were evaluated with HE, PASM,and masson trichrom staining and CK19 was detected by anti-CD19 antibody staining at each stage. Results The positive rate of AMA-M2 in model group at week 24 was 100%（5/5）,significantly higher than in the control group（0/5）;The percentages of CD4⁺CD25⁺Foxp³⁺ Tregs in the peripheral blood in model group at week 8,16 and 24 were（3.48±0.95）%,（3.30±1.55）% and（2.67±0.97）%,all of which significantly lower than those in the control group at each corresponding time[（7.25±1.63）%,（6.33±1.06）% and（5.58±1.52）%,P<0.05];The expression of CK19 in liver tissues showed no significant difference between the two groups;Liver pathology showed progressively increased infiltration of inflammatory cells around the portal area and bile duct,small bile duct proliferation,bilious fragmental necrosis and bridging fibers in model group. Conclusions The animal model of early PBC is successfully established by injection of Poly I:C and the CD4⁺CD25⁺Foxp3⁺ T cells may play a critical role in the pathogenesis of the entity.

Objective To evaluate the clinical value of laparoscopic fenestration for polycystic kidney complicated with polycystic liver. Methods The data of eight patients who received laparoscopic fenestration for polycystic kidney complicated with polycystic liver during January 2009 and February 2014 were collected and retrospectively analyzed. Results The procedures were successfully performed in all 8 cases,and no cases was conversed to open abdominal operation. The mean operating time was （96.31±14.26） min （70 to 120 min） without complications. The mean hospital stay were（4.89±0.76） days （4 to 6 days）. The average followed-up period after operation were（18.52±5.03） months（8 to 24 months）. The symptom of abdominal pain was improved and high blood pressure decreased in all 8 cases. The serum creatinine,blood urea nitrogen and cystatin C levels were significantly decreased in 5 cases,while in 3 cases had no significant improvement in renal function. ConclusionsThe laparoscopic fenestration for polycystic kidney complicated with polycystic liver has advantages of less injury,shorter hospital stay and significantly improved clinical symptoms, which may worth the clinical application.

Objective To investigate the expression of histidine-rich glycoprotein（HRG） in hepatocellular carcinoma（HCC） and its impact on HCC cell proliferation. Methods Immunohistochemistry was used to detect the expression of HRG in 8 HCC specimens and Western blot to evaluate the expression of HRG in 11 surgical cancerous and its non-cancerous specimens. The cell proliferation was analyzed by flow cytometry after stable overexpression of HRG in MHCC-97H cells. Results Declined expression of HRG was found in all 8 cancerous tissues as compared to the non-tumor tissues;Similar results were obtained in 11 pairs of HCC and its para-carcinoma tissues;The relative expression of HRG/β-actin was（1.39±2.08） in para-carcinoma tissues, and （0.14 ± 0.17） in tumor tissue,with a significant difference between them（P<0.05）;The cell proliferation of MHCC-97H cells overexpressing HRG was remarkably inhibited as compared with the mock cells[（1.72±1.19）% vs.（14.3± 2.99）%,P<0.01]. Conclusion HRG is down-regulated in HCC and HRG overexpression can inhibit HCC cell proliferation in vitro.

DILI is the most important cause of acute liver failure in the U.S. The emerging concept of drug-specific “upstream” events that cause initial hepatocyte injury and less specific“downstream” events described by Kaplowitz,which provides clear direction for further DILI mechanism research. Currently,it’s well-know that the mechanism of DILI is complex,involving drug metabolism, mitochondrial dysfunction,immune response,signal transduction,genetic and environmental et al. Progression of DILI may be the result of the combined effects of multiple factors.

Programmed death-1（PD-1） is an important coordinated stimulus molecule belonging to the B7/CD28 family. When it combines with its ligand programmed death ligand （PD-L）,can regulate the activation,differentiation and multiplication of T lymphocytes. PD-1 expression in different stages of chronic HBV infection varies,and is closely related to the degree of liver inflammation,ALT levels and viral loads. Through different ways to block the PD-1/PD-L1 pathway can improve the function of T lymphocytes,and it might be one of the direction for antiretroviral treatment in the future.

Liver failure caused by many etiologies,is a deficiency of liver. Its pathogenesis still remains unclear, and it might involve necrosis,apoptosis and regeneration of the hepatocytes,and fibrosis of the liver. As a kind of pattern recognition receptor,Toll-like receptors（TLRs） link the innate and adaptive immune response,and play an important role in the pathogenesis of liver failure. Animal experiments and clinical studies have demonstrated that TLRs are related to the necrosis of liver cells. Liver injury which is caused by different agents,such as LPS,D-GalN, ConA,CpG ONA,Poly（I:C）and APAP,needs different TLRs signaling. TLR3,TLR4 and TLR9 signaling can promote apoptosis of liver cells. TLR7 signaling has a protective effect against liver fibrosis. Research on TLR polymorphism can reveal the pathogenesis of liver failure from the host aspect, and provide evidences for individualized diagnosis and treatment of patients with liver failure.

Immune disturbance plays an important roles in the pathogenesis and development of viral hepatitis and liver cirrhosis. Many inflammatory cytokines and complement components have become highlights in this field. Abnormal complement balance has been found in many liver diseases,such as viral hepatitis, autoimmune liver disease,alcoholic liver disease and so on. We discuss some hotspots in this review.

Malnutrition in patients with liver cirrhosis is an important factor affecting the prognosis and mortality of these patients. In recent years,several nutritional evaluation methods are used in clinical practice, such as the body energy and substance metabolism assessment,anthropometric,biochemical and immunological indexes,and imaging evaluation. In this review, we summarized the application of these methods in order to provide references for assessing the nutritional status.