IgG4- related diseases are a class of chronic, progressive, systemic inflammatory disorders that are characterized by lymphoplasmacytic inflammation, as well as elevated IgG4 levels in serum and tissue, and may involve multiple organs or tissues. When involving the pancreas, liver, and biliary tracts, they are called IgG4- related hepatobiliary diseases. IgG4- related autoimmune pancreatitis, IgG4- related sclerosing cholangitis, and IgG4- associated autoimmune hepatitis are reviewed in terms of their clinical manifestations and laboratory findings. Accurate identification of the laboratory results for IgG4- related hepatobiliary diseases and correct diagnosis of these diseases help to avoid unnecessary surgery and wrong treatment.

Primary biliary cirrhosis ( PBC) is characterized by injury of small intrahepatic bile ducts, but its mechanism, especially the role of B cell immunity in this disease, remains unclear. The possible role of B cell immunity in the pathogenesis of PBC is reviewed from the following aspects: distribution of B cells and plasma cells in the liver tissues of PBC patients, clearance of B cells, mechanism of abnormal increase in serum IgM and its sources among PBC patients, mechanism of production of antimitochondrial antibodies and their possible functions in bile duct injury, and typical autoantibodies in PBC. B cell immunity is considered to play a significant role in the pathogenesis of PBC, but there are still many key problems to be clarified.

Objective To investigate the clinical significance of combined antigen screening reagents for autoimmune liver disease ( AILD) . Methods A total of 140 patients with liver diseases who visited the Beijing You'an Hospital affiliated to Capital Medical University from September 2011 to September 2012, as well as 30 healthy blood donors and 8 relatives of patients with primary biliary cirrhosis ( PBC) , were included in the study. The serum samples from the 178 subjects were tested by enzyme- linked immunosorbent assay ( ELISA) for detection of AMA- M2, anti- sp100 antibodies, anti- gp210 antibodies, anti- LKM- 1 antibodies, and anti- SLA / LP antibodies, as well as indirect immunofluorescence assay ( IFA) for autoantibodies, immunoblotting ( IB) for antibody profiles, and AMA- M2 ELISA. Results Of the 140 patients tested by screening reagents, 70 ( 50%) had positive results, and 49 of them had strong positive results. Of the 70 positive cases, 61 were positive for ANA and 63 were positive for AMA, as shown by IFA; 21 of the 61 ANA- positive cases had a rim pattern of staining. The IB showed that 16 cases were positive for anti- gp210 antibodies, and 5 cases were negative. The AMA- M2 ELISA showed that 60 of the 63 AMA- positive cases were positive for AMA- M2. Of the 49 strong positive cases, 2 were positive for anti- gp210 antibodies, 5 for anti- sp100 antibodies, 20 for AMA- M2, 12 for both anti- gp210 antibodies and AMA- M2, and 10 for both anti- sp100 antibodies and AMA- M2, as shown by conventional tests. Among the 178 subjects, all the 65 PBC patients were positive for PBC- related antibodies by conventional tests, while 63 of these PBC cases had positive results using the screening reagents, with a coincidence rate of 96. 9% ( 63 /65) ; the number of positive cases detected using conventional reagents was insignificantly higher that determined by screening reagents ( χ2= 0. 016, P > 0. 05) . Four cases tested positive for autoantibodies using screening reagents, but had negative results using conventional reagents. Conclusion The combined antigen screening reagents for AILD have the advantages of high sensitivity, high specificity, easy operation, high efficiency, and low cost, and they can be used in the preliminary screening for AILD.

Objective To investigate the changes in frequencies of peripheral blood lymphocyte ( PBL) subsets and their clinical significance in patients with primary biliary cirrhosis ( PBC) , autoimmune hepatitis ( AIH) , and AIH- PBC overlap syndrome. Methods Forty- one patients with AIH- PBC overlap syndrome, 37 patients with AIH, 36 patients with PBC, and 50 healthy persons were included in the retrospective study. The frequencies of PBL subsets were determined by flow cytometry. The changes in frequencies of PBL subsets and their clinical significance were investigated. Results Compared with the healthy control group, the AIH- PBC group, PBC group, and AIH group had a significantly increased frequency of CD3+CD4+T cells and a significantly decreased frequency of CD3-CD16+CD56+NK cells; the PBC group and AIH- PBC group had significantly increased CD4+/ CD8+ratio and frequency of CD3-CD19+B cells and a significantly decreased frequency of CD3+CD8+T cells. During different stages of diseases, in the AIH- PBC group and PBC group, the frequencies of CD3+T cells and CD3+CD8+T cells were significantly lower in patients with liver cirrhosis than in those without liver cirrhosis. Conclusion The changes in frequencies of PBL subsets are related to the progression of autoimmune liver diseases, providing important immunological parameters for clinical evaluation of the immune status in patients with autoimmune liver diseases.

Objective To analyze the clinical features and laboratory test results of patients with autoimmune hepatitis ( AIH) - primary biliary cirrhosis ( PBC) overlap syndrome, as well as their correct diagnosis rate and time to diagnosis. Methods Fifty- three patients who were diagnosed by liver biopsy as having AIH- PBC overlap syndrome from January 2009 to June 2013 were selected as subjects; 53 AIH patients and 53 PBC patients were selected as control groups. Their clinical manifestations, laboratory test results, and diagnosis on admission were retrospectively analyzed. Comparison of normally distributed quantitative data between groups was made by one- way analysis of variance, and multiple comparisons were made by SNK- q test; comparison of qualitative data between groups was made using R × C contingency table, and multiple comparisons were made by Scheffe's confidence interval test. Results The 53 patients with AIH- PBC overlap syndrome had a serum alanine aminotransferase level of 173. 65 ± 52. 08 U / L, a serum total bilirubin level of 38. 07 ± 6. 82 μmol / L, a serum alkaline phosphatase ( ALP) level of 293. 81 ± 28. 89 U / L, and a serum gamma- glutamyl transpeptidase level of 57. 57 ± 78. 84 U / L. ALP showed significant difference between the patients with AIH- PBC overlap syndrome and control groups. The serum level of immunoglobulin M in overlap syndrome patients was 3. 33 ± 2. 12 g / L, which was significantly different from those of two control groups. Of the 53 overlap syndrome patients, 27 were positive for anti- mitochondrial antibody- M2, and the positive rate was significantly different from those of two control groups. Without liver biopsy, the correct diagnosis rate was the lowest ( 52. 83%) , and it took the longest time ( 8 ± 7. 7 d) to confirm the diagnosis on admission. Conclusion The clinical manifestations of patients with AIH- PBC overlap syndrome are more similar to those of PBC patients, but their biochemical test results are more similar to those of AIH patients. AIH- PBC overlap syndrome has the clinical features of both AIH and PBC.

Objective To investigate the clinical value of serum soluble intercellular adhesion molecule- 1 ( sICAM- 1) in patients with primary biliary cirrhosis ( PBC) and autoimmune hepatitis ( AIH) . Methods Sixty- one PBC patients and 59 AIH patients, who were hospitalized or visited the outpatient department from June 2012 to September 2013, as well as 50 healthy controls, were included in the study. The PBC patients included 29 incipient cases, 21 cases in remission, and 11 recurrent cases; the AIH patients included 26 incipient cases, 20 cases in remission, and 13 recurrent cases. Serum sICAM- 1 level was measured by double- antibody sandwich enzyme- linked immunosorbent assay, and serum levels of alanine aminotransferase ( ALT) and total bilirubin ( TBil) were determined by biochemical enzyme assay. Comparison between groups was made by analysis of variance; Pearson correlation analysis was performed. Results Among PBC patients, the incipient group and recurrent group had significantly higher serum sICAM- 1 levels than the remission group and control group ( P = 0. 000 for all) ; there was no significant difference in serum sICAM- 1 level between the incipient group and recurrent group ( P = 0. 484) ; the remission group had a significantly higher serum sICAM- 1 level than the control group ( P = 0. 000) . Among AIH patients, the incipient group and recurrent group had significantly higher serum sICAM- 1 levels than the remission group and control group ( P = 0. 000 for all) ; there was no significant difference in serum sICAM- 1 level between the incipient group and recurrent group ( P = 0. 802) ; no significant difference in serum sICAM- 1 level was seen between the remission group and control group ( P = 0. 281) . For patients with PBC and AIH, serum sICAM- 1 level was positively correlated with serum levels of ALT ( r = 0. 664, P = 0. 000; r = 0. 784, P = 0. 000) and TBil ( r = 0. 715, P = 0. 000; r = 0. 580, P = 0. 000) . Conclusion Serum sICAM- 1 may be involved in the immunologic injury in PBC and AIH. In patients with PBC and AIH, the elevation of serum sICAM- 1 level is closely correlated with the severity of liver damage. Clinical monitoring of serum sICAM- 1 level may play an important role in severity assessment, prognostic evaluation, and therapy guidance among patients with autoimmune liver diseases.

Objective To investigate the diagnostic value of FibroTest combined with FibroScan for liver fibrosis in patients with chronic hepatitis B ( CHB) . Methods Serum samples were collected from 99 CHB patients who underwent liver biopsy in Tianjin Second People's Hospital from August 2011 to July 2013. Serum levels of α2- macroglobulin, haptoglobin, apolipoprotein AI, total bilirubin, and gamma-glutamyl transpeptidase were measured, and FibroTest scores were calculated according to the measurement results, as well as the age and sex of patients. In addition, all patients underwent liver stiffness measurement by FibroScan. According to the Scheuer system, liver fibrosis was staged as significant fibrosis ( S2- S4) and severe fibrosis ( S3- S4) . With liver biopsy as the gold standard, the areas under the receiver operating characteristic curves ( AUCs) of FibroTest and FibroScan were determined. The diagnostic values of FibroTest and FibroScan for liver fibrosis in CHB patients were evaluated accordingly, and their combined diagnostic value was determined by logistic stepwise regression analysis. Results The AUCs of FibroTest and FibroScan for the prediction of significant fibrosis ( S2- S4) were 0. 805 ( 95% CI: 0. 713- 0. 897, P < 0. 001) and 0. 896 ( 95% CI: 0. 833- 0. 959, P < 0. 001) , respectively, and their AUCs for the prediction of severe fibrosis ( S3- S4) were 0. 834 ( 95% CI: 0. 741- 0. 928, P < 0. 001) and 0. 945 ( 95% CI: 0. 891- 0. 999, P < 0. 001) , respectively. Their combined AUC for the prediction of significant fibrosis ( S2- S4) was 0. 911 ( 95% CI: 0. 854- 0. 967, P < 0. 001) . Conclusion The combination of FibroTest and FibroScan can evaluate the liver fibrosis in CHB patients more accurately, and it not only improves diagnostic specificity, but also ensures high diagnostic accuracy, providing guidance for the prognostic evaluation and treatment of CHB.

Objective To investigate the clinical efficacy of sequentially used duodenal endoscope electronic choled ochoscope and laparoscope in the treatment of choledocholithiasis with gallbladder stones. Methods A retrospective analysis was performed on 834 patients with choledocholithiasis and gallbladder stones who received treatment with sequentially used duodenoscope, laparoscope, and electronic choledochoscope in our hospital from June 1999 to June 2010. Results The 834 cases received treatment with two endoscopes, and 793 ( 95. 08%) had the stones successfully removed. The other 41 cases received secondary treatment with three endoscopes, and 39 ( 95. 12%) of them had the stones successfully removed. The two failed cases had severe adhesion at the porta hepatis and lesser omental foramen, which made bile duct exploration impossible, and were then treated by laparotomy. Complications were seen in 28 of the 834 cases. Conclusions Treatment with sequentially used endoscopes is feasible and safe and causes few complications in patients with choledocholithiasis and gallbladder stones, and it holds promise for clinical application.

Objective To investigate the characteristics of high- risk cholecystolithiasis and summarize the experience of laparoscopic cholecystectomy for this disease. Methods A retrospective analysis was performed on the clinical data of 115 patients with high- risk cholecystolithiasis who underwent laparoscopic cholecystectomy in our hospital from October 2008 to March 2012. Results Of the 115 patients, 47 had stones filling the gallbladder as well as atrophy of the gallbladder and porcelain gallbladder, 42 had acute suppurative and gangrenous cholecystitis, 20 had stone incarceration in the gallbladder neck, 3 had cystic duct stones, 2 had cholecystoduodenal fistula, and 1 had Mirizzi syndrome; all patients were cured and discharged. Conclusion For patients with high- risk cholecystolithiasis, laparoscopic cholecystectomy is feasible, given active preoperative preparation, strengthened perioperative management, and accurate, standard, and skilled surgical operation.

Objective To evaluate the safety and clinical effect of albumin dialysis combined with plasma perfusion in the treatment of liver failure. Methods Seventeen patients with liver failure were treated with albumin dialysis combined with plasma perfusion from January 2010 to April 2012. The treatment outcomes were evaluated based on the changes in routine blood results, biochemical indices, and blood coagulation indices, as well as clinical manifestations and vital signs. Comparison of means before and after treatment was made by paired t- test. Results The patients showed no significant changes in levels of hemoglobin, platelet, and fibrinogen after treatment ( P > 0. 05 for all) . After treatment, all patients showed variable improvements in clinical symptoms including weakness, poor appetite, abdominal distension, and low spirit. The patients had significantly decreased levels of total bilirubin ( t = 12. 74, P < 0. 01) , creatinine ( t = 4. 74, P < 0. 01) , and blood ammonia ( t = 7. 22, P < 0. 01) after single treatment. Of the patients with hepatic encephalopathy, 71% showed improvements, and 60% of patients with hepatorenal syndrome showed improvements. Among all patients, 64. 7% were cured or showed improvements when discharged. Conclusion Albumin dialysis combined with plasma perfusion is safe and effective in the treatment of liver failure, especially for patients with hepatic encephalopathy and hepatorenal syndrome.

Objective To analyze the clinical characteristics of drug- induced liver injury ( DILI) . Methods A retrospective analysis was performed on the clinical data of 394 patients with DILI who were admitted to our hospital from 2009 to 2011. The studied factors included age, sex, names and categories of toxic drugs, time of onset, liver function, whether liver biopsy was performed, treatment, and prognosis. Results There is an upward trend in cases of DILI. Among the 394 patients with DILI, 170 ( 43. 15%) were males, and 224 ( 56. 85%) were females; the male- to- female ratio was 1∶ 1. 3; the peak ages were 41- 50 years ( 25. 63%) and 51- 60 years ( 25. 13%) . A variety of drugs could cause DILI, with traditional Chinese medicines ( TCMs) ( 45. 43%) as the most common one, followed by a combination of drugs ( 11. 42%) and antitubercular drugs ( 7. 61%) . The TCM category mainly included those for treating osteoarthrosis ( 11%) and dermatosis ( 11%) , and the drug names and components were mostly unknown. Forty- three cases ( 10. 91%) were confirmed by pathological examination, and the common pathological changes included infiltration of neutrophils and eosinophils ( 65. 01%) and cholestasis of capillary bile ducts ( 39. 93%) , which had no specificity for clinical diagnosis, but provided some hint. Among the 394 patients, 102 ( 25. 89%) were cured, 184 ( 46. 70%) showed an improvement, and 7 ( 1. 78%) progressed to liver failure and death. The overall prognosis was good; the prognostic factors included age, clinical classification, and peak level of total bilirubin. Conclusion A variety of drugs can cause DILI, which has no specific clinical manifestations and gold diagnostic criteria, often leading to misdiagnosis; most cases have good prognosis, but liver failure may occur in some cases.

Objective To construct and identify the specific interference vector for second mitochondria- derived activator of caspase ( SMAC) gene in mice and perform lentiviral packaging. Methods According to the SMAC gene sequences in mice, three small interfering RNAs ( siRNAs) ( siRNA1, siRNA2, and siRNA3) and one negative control sequence ( siRNAn) were designed and synthesized, and mouse hepatocytes were transfected with the above siRNAs using Lipofectamine 2000. The inhibitory effects of these siRNAs on SMAC mRNA expression were evaluated by real- time PCR, and the optimal siRNA was screened out accordingly. Oligo DNA was synthesized based on the optimal siRNA and then connected to GV115 vector to obtain recombinant interference plasmid. The candidate clones were identified by PCR and sequenced. The recombinant interference plasmid, as well as pHelper 1. 0 and pHelper 2. 0, was used to transfect 293T cells for lentivirus packaging. Then, cell supernatants were collected and concentrated, and the lentiviral titer was determined by gradient dilution. Comparison between groups was made by analysis of variance, and multiple comparisons were made by SNK- q test. Results The three siRNAs had different inhibitory effects on SMAC mRNA expression in hepatocytes; siRNA1 showed the strongest inhibitory effect, with an inhibition efficiency of 70. 3%. Based on siRNA1, the oligo DNA was successfully synthesized and correctly connected to the lentiviral vector, as proved by sequencing. The lentiviral titer was 6 × 108TU / ml, as determined by gradient dilution. Conclusion The recombinant lentivirus that inhibits SMAC expression in mice has been constructed successfully, laying the foundation for further studies on the role of SMAC gene in liver failure.

Autoimmune liver disease ( AILD) is substantially different from common liver diseases, and it is very important to improve its recognition and diagnostic level. The literature on AILD published in recent years is reviewed, and the advances in pathogenesis, autoantibodies, diagnosis, and treatment of AILD are summarized. However, it is pointed out that further clinical research and practice are needed for better diagnosis and treatment of AILD.

Primary biliary cirrhosis ( PBC) is an autoimmune disease. Ursodeoxycholic acid ( UDCA) is the only safe and effective drug for the treatment of PBC, as proved by randomized controlled clinical trials, so it is advocated as first- line therapy. Alternative therapies are urgently needed for patients with poor response to UDCA. In addition to the efficacy of UDCA, the classification of alternative and adjuvant therapies for UDCA nonresponders and the latest research progress in these therapies are reviewed; the efficacy of existing drugs and treatment prospects are evaluated, but more long- term clinical studies are needed to confirm the efficacy of immunosuppressants such as budesonide and etanercept and other drugs. A number of novel molecular therapies for PBC are also undergoing clinical trials. There is currently no consensus on the medical treatment for patients with poor response to UDCA. Although studies have shown that some drugs can improve liver function and liver biochemistries, there is no definitive evidence that they improve long- term outcome.

Primary biliary cirrhosis ( PBC) is a chronic disease characterized by progressive destruction of intrahepatic small bile ducts, which may progress to liver cirrhosis. Anti- mitochondrial antibodies, especially anti- M2 antibody, have a high diagnostic value for PBC, but they are unrelated to the severity and prognosis of the disease and are negative in some patients. There have been reports from around the world that anti- nuclear antibodies, especially anti- gp210 antibody, are closely associated with PBC. It showed that anti- gp210 antibody has high specificity and sensitivity for the diagnosis of PBC, especially for the patients with negative anti- M2 antibody tests; in addition, it has a high predictive value for the prognosis and development model of the disease. Anti- gp210 antibody has a high diagnostic value for PBC, with great clinical significance, so its detection holds promise for clinical application.

Nonalcoholic fatty liver disease ( NAFLD) is the most common progressive liver disease worldwide. Currently, there is no satisfying treatment for NAFLD. Research progress in fatty acid bile acid conjugates ( FABACs) and ursodeoxycholyl lysophosphatidylethanolamide ( UDCA- LPE) , which are two novel liver targeted drugs with anti- NAFLD effects, is reviewed. FABACs, which reduce liver fat in patients with NAFLD induced by high- fat diet by regulating lipid metabolism, have been proved effective in preventing and treating NAFLD. The safety and efficacy of FABACs in NAFLD patients have been confirmed in a phase II, randomized, double- blind, placebo- controlled trial. UDCA- LPE can not only reduce liver fat in NAFLD patients, but also inhibit mitochondrial damage and apoptosis and promote hepatocyte regeneration, with a marked anti- inflammatory effect during the development of NAFLD. Therefore, FABACs and UDCA- LPE hold promise for preventing and treating NAFLD.

MicroRNA- 122 ( miR- 122) , a liver- specific microRNA, has important functions in the physiological function and disease development of the liver. The association of miR- 122 with steatohepatitis and its possible action mechanism are described, and the effects of altered miR- 122 expression in regulating infections with hepatitis B virus and hepatitis C virus are discussed. In addition, the roles of miR- 122 in the development and progression of hepatocellular carcinoma are summarized. It is thought that the functions of miR- 122 in the liver provide a new target and therapeutic strategy for treatment of liver diseases.