With the successful application of direct-acting antivirals (DAAs) in the treatment of hepatitis C, clinical management of drug-drug interaction (DDI) has become a hot topic in this field.Most DAAs develop DDI with other drugs administered at the same time via cytochrome P450 or transporters in the liver and/or the intestine.At present, European Association for the Study of the Liver has published the recommendations on DDI of DAAs in the treatment of chronic hepatitis C, which covers HIV antiretrovirals, lipid-lowering drugs, cardiovascular drugs, immunosuppressants, and addictive drugs for the central nervous system.When developing the regimens for DAA treatment, clinicians should closely assess and monitor the risk of DDI, in order to reduce or avoid treatment failure or adverse reactions during antiviral therapy.

Chronic hepatitis C (CHC) is a chronic and progressive disease prevalent in the whole world and greatly threatens human health.The launch of direct-acting antiviral agents (DAAs) brings a revolutionary change in the treatment of CHC.In recent years, several DAAs have been marketed in foreign countries and have achieved good clinical effects, and in China, some DAAs have also been approved and widely used in clinical practice, which contributes to the increase in the cure rate of hepatitis C.This article analyzes the features, clinical effects, and indications of DAAs marketed in China and reviews published real-world studies, in order to help clinicians select proper treatment regimens based on patients' features.

Dual infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) has significantly different clinical, immunological, and virological features from single infection with HCV or HBV, which brings various challenges to clinical diagnosis/treatment and management.Direct-acting antiviral agents used for effective control of HCV infection may cause HBV activation, onset of hepatitis B, and even liver failure.Therefore, during the antiviral treatment of HCV infection, it is of great importance to select appropriate anti-HBV therapy and follow-up management strategies based on the status of HCV/HBV dual infection.

Chronic Hepatitis C is a global epidemic, and people with different sexes, ages, races, and nationalities are susceptible to hepatitis C virus (HCV) infection.This article elaborates on the management method and individualized treatment regimens for special populations, including children with hepatitis C, patients with renal injury, patients undergoing liver transplantation, patients with liver cirrhosis, patients with HIV infection, and patients with acute hepatitis C.

Chronic hepatitis C in children has an insidious onset and has few available treatment options.Pegylated interferon alpha (Peg-IFNα) combined with ribavirin (RBV) , known as the PR regimen for short, used to be the standard regimen; however, treatment response is often affected by various factors including hepatitis C virus genotype, viral load, and host gene polymorphisms, and some children cannot tolerate the adverse reactions of PR regimen.HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C developed by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD/IDSA) in September, 2017 recommended that direct-acting antiviral agents (DAAs) can be used for children with hepatitis C who are aged above 12 years or have a body weight of ≥35 kg.Sofosbuvir combined with ledipasvir is the recommended regimen for children with genotype 1, 4, 5, or 6 infection, and sofosbuvir combined with RBV is recommended for children with genotype 2 or 3 infection.The course of disease is 12 weeks for previously untreated children with genotype 1 infection, children with genotype 1 infection who were treated by IFNα and do not have liver cirrhosis, or children with genotype 2, 4, 5, or 6 infection, and 24 weeks for children with genotype 1 infection who were treated by IFNαand have liver cirrhosis or children with genotype 3 infection.Further studies are needed to investigate the type of DAAs used in children with chronic hepatitis C aged < 12 years, related regimens, and their safety.As for special populations including children with chronic hepatitis C complicated by HIV infection and those treated by liver transplantation, individualized treatment regimens should be developed with reference to the status of HIV infection and complications of liver transplantation.

The incidence of hepatitis C virus infection is commonly seen in patients with renal dysfunction (RD) , especially those with end-stage renal disease on hemodialysis (HD) , among whom the incidence and mortality of liver diseases increase.The development of direct-acting antiviral agents has revolutionized the therapy for chronic hepatitis C (CHC) with a sustained virologic response rate of > 90% and a low rate of adverse events.Grazoprevir/elbasvir, paritaprevir/ritonavir + ombitasvir + dasabuvir, glecaprevir/pibrentasvir, or daclatasvir + asunaprevir regimen is recommended in CHC patients with RD and HD, while the sofosbuvir-based regimen is not recommended.

Objective To investigate the efficacy and safety of interferon-α (IFN-α) given additionally or sequentially after effective inhibition of HBV DNA by long-term entecavir (ETV) therapy versus ETV alone in the treatment of chronic hepatitis B (CHB) .Methods A total of 27 CHB patients with negative HBV DNA who were admitted to department of infectious diseases in Wujiang Hospital Affiliated to Nantong University from January 2013 to December 2015 had been treated with ETV antiviral therapy for 3 or more years and had no contraindications for IFN-α therapy were enrolled and randomly divided into three groups, with 9 patients in each group.The patients in the control group were given ETV alone, those in sequential group were given IFN-α sequentially after ETV therapy, and those in the combination group were given IFN-α additionally after ETV therapy.Serum HBV DNA, HBV serum markers, routine blood test, and liver function were measured at 0, 12, 24, 36, and 48 weeks of treatment.The patients' treatment outcomes were observed and a statistical analysis was performed.A one-way analysis of variance was used for comparison between multiple groups, and the Scheffe test was used for further comparison between two groups.Results There were not drop-outs, and no patient experienced serious adverse reactions.One patient in the sequential group experienced viral rebound after 24 weeks of treatment without any clinical symptoms and had normal liver function parameters.At the end of treatment, the sequential group and the combination group had a significantly higher absolute value of the reduction in HBsAg than the control group (both P < 0.001) .Two patients each in the sequential group and the combination group achieved HBsAg clearance, resulting in a clearance rate of 22%.No patient in the control group achieved HBsAg clearance.Conclusion IFN-α given additionally or sequentially after effective inhibition by ETV is safe and may achieve a significantly greater reduction in HBsAg than ETV alone.A few patients even achieve clinical cure.

Objective To investigate the antiviral effect of tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) in the treatment of treatment-nave patients with chronic HBV infection.Methods A total of 420 treatment-nave patients with chronic HBV infection or liver cirrhosis who received antiviral therapy with TDF or ETV and were regularly followed up in Zhoukou Central Hospital or Bayi Hospital Affiliated to Nanjing University of Chinese Medicine from July 2014 to July 2015 were enrolled, and among these patients, 184 received TDF (TDF group) and 236 received ETV (ETV group) .Laboratory markers were measured at baseline and at weeks 4, 8, 12, 24, and 48 of treatment, including liver and renal function parameters, blood calcium, serum phosphate, creatine kinase, HBV DNA level, hepatitis markers (HBs Ag, HBeAg, and anti-HBe) .Adverse drug reactions were also monitored.The t-test was used for comparison of continuous data between groups, and the chi-square test or Fisher's exact test was used for comparison of categorical data between groups.Results At week 48 of treatment, there were no significant differences between the two groups in HBeAg clearance rate among both HBeAg-positive patients and HBeAg-positive patients with HBV DNA > 6 lg IU/ml (P > 0.05) .There were also no significant differences between the two groups in alanine aminotransferase normalization rate among HBeAg-negative patients, HBeAg-positive patients, and HBeAg-positive patients with HBV DNA > 6 lg IU/ml (P > 0.05) .Both groups had a gradual reduction in HBV DNA level after the antiviral therapy.At week 48 of treatment, there were significant differences between the TDF group and the ETV group in the proportion of patients with a HBV DNA level below the lower limit of detection among HBeAg-positive patients (75.5% vs 60.8%, χ2= 5.857, P = 0.016) and HBeAg-positive patients with HBV DNA > 6 lg IU/ml (75.7% vs 60.5%, χ2= 5.722, P = 0.017) .At week 96 of treatment, the TDF group had a significantly higher rate of HBV DNA below the lower limit of detection than the ETV group among all patients (93.5% vs 86.9%, χ2=4.921, P = 0.027) , HBeAg-positive patients (89.1% vs 76.2%, χ2= 6.781, P = 0.009) , and HBeAg-positive patients with HBV DNA > 6 lg IU/ml (88.3% vs 73.7%, χ2= 7.456, P = 0.006) .Conclusion In HBeAg-positive patients with chronic HBV infection, TDF has a better inhibitory effect on HBV DNA than ETV, especially in those with HBV DNA > 6 lg IU/ml.

Objective To investigate the correlation of the expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 3 (TLR3) in live tissue with the grade of liver inflammation and degree of liver fibrosis and related clinical significance in patients with chronic hepatitis B (CHB) .Methods A total of 104 patients who were hospitalized in Department of Hepatology, The Third People' s Hospital of Guilin, from January 2013 to December 2016 and were diagnosed with CHB were enrolled.Liver biopsy was used to obtain liver tissue samples from CHB patients, and immunohistochemical staining of TLR2 and TLR3 was performed.Normal adjacent liver tissue samples collected from 10 patients with hepatic hemangioma were used as controls.The correlation of TLR2 and TLR3 with the grade of liver inflammation and degree of liver fibrosis was analyzed.The Kruskal-Wallis H test was used for comparison between multiple groups, Spearman correlation analysis was used to investigate correlation.Results There was no marked positive expression of TLR2 and TLR3 in the control group.There was weak expression of TLR2 in the liver tissue of CHB patients, and the expression of TLR21 was not correlated with the grade of liver inflammation or the degree of liver fibrosis (rs=-0.086 and-0.112, both P > 0.05) .There was strong expression of TLR3 in the liver tissue of CHB patients, and the expression of TLR3 was significantly positively correlated with the grade of liver inflammation (rs= 0.528, P <0.01) ; TLR3 also had a linear relationship with the grade of liver inflammation (χ2= 16.679, P < 0.01) .Conclusion TLR3 may be involved in the immune pathogenesis of CHB and the pathological process of liver fibrosis.

Objective To investigate the detection rate and features of autoantibodies in chronic hepatitis C (CHC) patients after plasmaphoresis, as well as the liver pathological features of autoantibody-positive CHC patients.Methods A total of 120 patients who were infected with hepatitis C virus after plasmaphoresis in the Hospital of Dingxi County and Dingxi Hospital of Infectious Diseases from January1992 to December 1995 were selected as test group; 11 healthy people from the same region were selected as control group.Autoantibody detection was performed for the 120 CHC patients, and liver pathological features were compared between the autoantibody-positive group (n = 44) and autoantibody-negative group (n = 76) of these patients.The t test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data.Results Of all 120 CHC patients who underwent plasmaphoresis, 44 (36.7%) were found to have serum autoantibodies, with antinuclear antibodies as the most common type (21.7%) .Compared with the autoantibody-negative group, the autoantibody-positive group had significantly higher scores of focal necrosis inside the hepatic lobules (2.11 ± 0.88 vs 1.64 ±0.88, t = 2.349, P = 0.021) and ductular reaction inside the portal area (1.86 ± 0.71 vs 1.13 ± 0.66, t = 4.217, P < 0.001) , as well as a significantly higher rate of interlobular bile duct injury (86.4% vs 55.3%, χ2= 12.129, P = 0.001) .There were no significant differences between the two groups in the degree of liver fibrosis and hepatic steatosis (both P > 0.05) .Conclusion Autoantibody-positive are common in CHC patients after plasmaphoresis, and autoantibody-positive patients tend to have more severe injuries of the liver.

Objective To investigate the influence of the Notch signaling pathway on CD8+T lymphocyte function in patients with chronic hepatitis C (CHC) and the role of the Notch signaling pathway in the pathogenesis of CHC.Methods A total of 38 treatment-na6 ve CHC patients who visited Shaanxi Provincial People's Hospital from January to August, 2016 and 17 healthy volunteers were enrolled in this study.CD8+T lymphocytes were isolated, and quantitative real-time PCR was used to measure the mRNA expression of Notch1 and Notch2 in CD8+T lymphocytes.CD8+T lymphocytes, which were isolated from HLA-A2-restricted CHC patients, were co-cultured with hepatitis C virus (HCV) -infected Huh7.5 cells in both direct and indirect contact culture systems.DAPT, a Notch signaling pathway inhibitor, was added, and the changes in cytotoxic and non-cytotoxic functions of CD8+T lymphocytes were analyzed by measuring the levels of lactate dehydrogenase level and cytokines.The t-test was used for comparison of continuous data between groups.Results The mRNA expression of Notch1 and Notch2 in CD8+T lymphocytes in CHC patients was 10 and 4 times, respectively, that in healthy volunteers (t = 6.63, P = 0.003; t = 18.88, P < 0.001) .Inhibition of the Notch signaling pathway significantly increased the percentage of dead cells in the direct contact culture system (26.41 ± 4.76% vs 13.65 ± 4.65%, t = 3.32, P = 0.029) , while it did not influence the cytotoxity of CD8+T lymphocytes in the indirect contact culture system.After inhibition of the Notch signaling pathway, there was a significant increase in the expression of interferon-γ in the direct (52.19 ± 12.38 pg/ml vs 18.62 ± 5.66 pg/ml, t = 4.27, P = 0.013) and indirect contact culture systems (18.86 ± 3.09 pg/ml vs 5.52 ± 2.52 pg/ml, t = 5.79, P = 0.004) .After inhibition of the Notch signaling pathway, there was a significant increase in the expression of tumor necrosis factor-α in the direct contact culture system (1296.0 ± 293.3 pg/ml vs 585.3 ± 32.62 pg/ml, t = 4.17, P = 0.014) , while there was no significant change in the indirect contact culture system (297.3 ± 175.4 pg/ml vs 273.7 ± 105.9 pg/ml, t = 0.20, P = 0.851) .Conclusion Inhibition of the Notch signaling pathway can enhance the cytotoxic and non-cytotoxic functions of CD8+T lymphocytes in CHC patients.The Notch signaling pathway may induce immune tolerance in chronic HCV infection by inhibiting the function of CD8+T lymphocytes.

Objective To investigate the value of albumin-bilirubin (ALBI) score combined with aspartate aminotransferase-to-platelet ratio index (APRI) in predicting the development of posthepatectomy liver failure (PHLF) in patients with HBV-related hepatocellular carcinoma (HCC) .Methods A retrospective analysis was performed for the patients with HBV-related HCC who underwent hepatectomy in The Affiliated Tumor Hospital of Guangxi Medical University from January 2006 to October 2013.With Child-Pugh score as control, the values of ALBI, APRI, and ALBI combined with APRI in predicting PHLF were analyzed.The chi-square test or the Fisher exact test was used for comparison of categorical data between groups, and the logistic regression model was used to identify independent predictive indices for PHLF.Results A total of 1055 patients were enrolled in this study, among whom 151 (14.3%) experienced PHLF.The univariate and multivariate analyses showed that ALBI and APRI were significantly associated with the prognosis of PHLF patients (P < 0.001) .ALBI and APRI had a significantly higher area under the receiver operating characteristic curve (AUC) than Child-Pugh score (both P<0.001) .albi="" had="" a="" sensitivity="" of="" and="" specificity="" in="" predicting="" phlf="" at="" the="" optimal="" cut-off="" value="" patients="" with="" albi="">-2.77 had a significantly higher incidence rate of PHLF A/B/C than those with ALBI ≤-2.77 (P < 0.001) .APRI had a sensitivity of 61.6% and a specificity of 71.0% in predicting PHLF at the optimal cut-off value of 0.85, and the patients with APRI >0.85 had a significantly higher incidence rate of PHLF A/B/C than those with APRI ≤0.85 (P < 0.001) .The combination of ALBI and APRI had a significantly higher AUC than ALBI or APRI (P < 0.001 and P = 0.047) .The combination of ALBI and APRI had a sensitivity of 78.1% and a specificity of 62.2% in predicting PHLF at the optimal cut-off value of-13.10, and the patients with the combination of ALBI and APRI >-13.10 had a significantly higher incidence rate of PHLF A/B/C than those with the combination of ALBI and APRI ≤-13.10 (P < 0.001) .Conclusion ALBI combined with APRI can be used as a new, convenient, and reliable index for predicting PHLF.

Objective To investigate the expression of interleukin-17 (IL-17) in hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC) with different levels of alpha-fetoprotein (AFP) , as well as its association with recurrence and prognosis after radical treatment for HCC.Methods A total of 167 patients with HBV-related HCC who underwent radical resection in The Affiliated Tumor Hospital of Xinjiang Medical University from January 2013 to December 2014 were enrolled, and 115 patients with hepatic hemangioma (including 83 HBV carriers) were enrolled as control group.ELISA was used to measure the serum level of IL-17 in 167 patients with HBV-related HCC, and electrochemical luminescence was used to measure the serum level of AFP.The correlation between the expression of IL-17 and the serum level of AFP was analyzed, as well as the association of the expression of IL-17 with recurrence and survival after radical resection of HCC.The chi-square test was used for comparison of categorical data between groups, and the Kaplan-Meier method, log-rank test, and Cox proportional hazards model were used for survival analysis.Results The patients with HBV-related HCC were divided into two groups according to the serum level of AFP, and there was a significant difference in the positive expression rate of IL-17 between AFP <400 ng/ml group and AFP≥400 ng/ml group [50.9% (58/114) vs 34.0% (18/53) , χ2= 8.11, P = 0.002]; there were also significant differences between these two groups in disease-free survival (34.1 months vs 13.4 months, χ2= 10.34, P < 0.05) , overall survival (84.2 months vs 57.4 months, χ2= 3.13, P < 0.05) , and tumor recurrence rate within 1 year (28.9% vs 50.9%, χ2= 10.89, P <0.05) .The Kaplan-Meier analysis showed that among the patients with HBV-related HCC and AFP < 400 ng/ml, the patients with positive expression of IL-17 had a significantly higher recurrence rate within 1 year after surgery than those with negative expression of IL-17, as well as significantly shorter disease-free survival and overall survival than those with low expression of IL-17 (χ2= 7.350, 3.814, and9.744, all P < 0.05) .The Cox proportional hazards model showed that positive expression of IL-17, tumor thrombus in vessels, and degree of tumor differentiation were influencing factors for the prognosis of HCC patients (all P < 0.05) .Conclusion For patients with HBV-related HCC and AFP < 400 ng/ml, positive expression of IL-17 indicates early recurrence and poor prognosis.

Objective To investigate the effect of enhanced recovery after surgery (ERAS) versus traditional rehabilitation program in patients undergoing hepatectomy.Methods Pub Med, EBSCO, MEDLINE, and Cochrane Library were searched for the articles on the effect of ERAS versus traditional rehabilitation program in liver surgery published up to August 2016.Two independent observers performed quality assessment and data extraction according to the inclusion and exclusion criteria, and Rev Man 5.3.5 was used for the Meta-analysis.Results A total of 4 articles with 524 patients (254 patients in ERAS group and 270 in traditional treatment group) were included.Compared with the traditional treatment group, the ERAS group had significantly shorter length of postoperative hospital stay (weighted mean difference[WMD]=-2.72, 95% confidence interval[CI]:-3.86 to-1.57, P<0.000 01) , shorter time to functional recovery (WMD =-2.67, 95% CI:-3.68 to-1.65, P < 0.000 01) , and lower overall incidence rate of complications (odds ratio [OR]= 0.45, 95% CI: 0.30-0.67, P < 0.000 1) .The subgroup analysis showed that the ERAS group also had significantly lower incidence rates of grade 1 and grade2-5 complications than the traditional treatment group (grade 1: OR = 0.55, 95% CI: 0.31-0.98, P < 0.05; grade 2-5: OR = 0.49, 95% CI: 0.32-0.76, P < 0.05) .There was no significant difference in rehospitalization rate between the two groups (P >0.05) .As for the level of C-reactive protein, there was no significant difference between the two groups at 1 and 3 days after surgery (P > 0.05) , but the ERAS group had a significantly lower level than the traditional treatment group at 5 days after surgery (WMD =-21.68, 95% CI:-29.30 to-14.05, P < 0.000 1) .The ERAS group also had a significantly shorter time to first flatus than the traditional treatment group (WMD =-0.93, 95% CI:-1.41 to-0.46, P = 0.000 1) .Conclusion ERAS is safe, effective, and feasible in liver surgery.

Objective To investigate the expression of the long non-coding RNA (lncRNA) XLOC-007123 in cancer and adjacent tissue, as well as hepatoma cell lines, in patients with hepatitis B-related hepatocellular carcinoma (HCC) , and the association between its expression level and clinicopathological features.Methods A total of 52 patients with hepatitis B-related HCC who underwent resection of HCC in Center of Hepatobiliary Surgery, 302 Hospital of PLA, from December 2013 to December 2015 were enrolled, and HCC tissue samples were collected.Adjacent tissue samples collected from the same patient were used as controls.Quantitative real-time PCR was used to measure the expression of the lncRNA XLOC-007123 in HCC tissue, adjacent tissue, and hepatoma cell lines in the patients with hepatitis B-related HCC.Normal liver cell line LO2 and hepatoma cell lines HuH7, HepG2, and SMMC-7721 were obtained from Research Center for Clinical and Translational Medicine, 302 Hospital of PLA.The nonparametric Wilcoxon rank sum test was used to compare the expression of the lncRNA XLOC-007123 between HCC tissue and adjacent tissue, and the independent samples t-test was used to compare the expression of the lncRNA XLOC-007123 between HCC cell lines and the normal liver cell line.The chi-square test was used for comparison of clinical indices.Results In the patients with hepatitis B-related HCC, the expression of the lncRNA XLOC-007123 was significantly lower in HCC tissue than in adjacent tissue (P < 0.01) ; also, the expression of the lncRNA XLOC-007123 was significantly lower in HuH7, HepG2, and SMMC-7721 cells than in LO2 cells (all P < 0.05) .The expression of the lncRNA XLOC-007123 was associated with the serum level of alpha-fetoprotein (AFP) and tumor stage (χ2= 7.738 and 7.589, both P < 0.05) .Conclusion There is a reduction in the expression of the lncRNA XLOC-007123 in hepatitis B-related HCC tissue, which is associated with the serum level of AFP and pathological staging, suggesting that the lncRNA XLOC-007123 may exert a regulatory effect in the development and progression of hepatitis B-related HCC and may become a potential marker for the diagnosis of hepatitis B-related HCC.

Objective To investigate the inhibitory effect of fibroblast growth factor-21 (FGF-21) on the carcinogenesis of L02 cells induced by diethylnitrosamine (DEN) .Methods L02 cells were cultured and treated with different concentrations of DEN (1, 10, 20, 50, 100, and 150 μmol/L) .MTT assay was used to measure the influence of DEN on the viability of L02 cells, and an appropriate stimulation concentration of DEN (20 μmol/L) was selected for further study.The malondialdehyde (MDA) and superoxide dismutase (SOD) detection kits were used to measure the levels of MDA and SOD in L02 cells treated by DEN (20μmol/L) and normal L02 cells.Then L02 cells were divided into model control group (treated with 20μmol/L DEN and PBS) , low-dose FGF-21 group (20 μmol/L DEN + 1 μmol/L FGF-21) , and high-dose FGF-21 group (20 μmol/L DEN + 2 μmol/L FGF-21) .The levels of MDA and SOD were measured after 12 hours of cell culture.Real-time PCR and Western blot were used to measure the expression of βKlotho (KLB) , and Western blot was used to measure the level of phosphorylated protein kinase B (p-AKT) .The t-test was used for comparison of continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups.Results There was a significant increase in the level of MDA and a significant reduction in the level of SOD after L02 cells were treated with DEN (t = 9.336 and 16.281, P = 0.011 and 0.004) .Compared with the model control group, the low-and high-dose FGF-21 groups had a significant reduction in the level of MDA and a significant increase in the level of SOD (P <0.05) , and compared with the low-dose FGF-21 group, the high-dose FGF-21 group had a significantly lower level of MDA and a significantly higher level of SOD (P = 0.030 and 0.042) , and there was a significant difference between two groups.The high-and low-dose FGF-21 groups had significantly higher mRNA expression of KLB than the model control group (P < 0.001) , and the high-dose FGF-21 group had significantly higher mRNA expression of KLB than the low-dose FGF-21 group (P < 0.001) , and there was a significant difference between two groups; the protein expression of KLB showed the same trend.The model control group had a significantly higher level of p-AKT than the other two groups (P < 0.05) , and the high-dose FGF-21 group had a significantly lower level of p-AKT than the low-dose FGF-21 group (P < 0.05) .Conclusion DEN can increase oxidative stress in L02 cells.By upregulating the expression of KLB, FGF-21 can reduce the level of p-AKT, inhibit oxidative stress in L02 cells induced by DEN, and thus inhibit the development of hepatocellular carcinoma.

Objective To investigate the value of serum and biliary carcinoembryonic antigen (CEA) , carbohydrate antigen 19-9 (CA19-9) , and carbohydrate antigen 24-2 (CA24-2) in the diagnosis of benign and malignant biliary obstructive diseases.Methods A total of 40 patients with benign biliary obstructive diseases and 40 with malignant ones, who were diagnosed and treated in The Central Hospital of Enshi Autonomous Prefecture from June 2015 to December 2016, were enrolled.Serum samples collected on admission and bile samples collected during surgery were used to measure the levels of tumor markers CEA, CA19-9, and CA24-2.The t-test was used for comparison between two groups, and a receiver operating characteristic (ROC) curve analysis was performed for each tumor marker in the diagnosis of benign and malignant biliary obstructive diseases.Results Compared with the benign group, the malignant group had significantly higher serum levels of CA19-9 and CA24-2 (t = 5.899 and 3.223, both P < 0.05) and biliary levels of CEA, CA19-9, and CA24-2 (t =3.304, 7.615, and 7.279, all P < 0.05) .In the patients with malignant biliary obstructive diseases, the levels of CEA, CA19-9, and CA24-2 in the bile were significantly higher than those in serum (t = 3.297, 4.975, and 3.993, all P < 0.05) .Biliary CA24-2 had the highest Youden index (0.75) and area under the ROC curve (AUC) (0.946) ; biliary CA19-9 had a Youden index of 0.74 and an AUC of 0.937, and serum CA19-9 had a Youden index of 0.68 and an AUC of 0.898.These three indices had a relatively high diagnostic value.Combined measurement of biliary CA24-2, serum CA19-9, and biliary CA19-9 had a sensitivity of 94.75%, a negative predictive value of 93.50%, and a Youden index of 0.82 in the diagnosis of malignant biliary obstructive diseases.Conclusion Biliary tumor markers have a great value in the diagnosis of malignant biliary obstructive diseases, and the combined measurement of biliary CA24-2, serum CA19-9, and biliary CA19-9 has the highest value in the differential diagnosis of benign and malignant biliary obstructive diseases.

Objective To investigate the effect of laparoscopic cholecystectomy on intraoperative and postoperative recovery and changes in serum levels of lipopolysaccharide (LPS) , amylase (AMY) , and adrenocorticotropic hormone (ACTH) after surgery in patients with acute cholecystitis (AC) .Methods A total of 98 patients with AC who were admitted to Xianyang Central Hospital from December 2015 to May2017 were enrolled, and according to the surgical procedure, these patients were divided into observation group and control group, with 49 patients in each group.The patients in the control group were given conventional open cholecystectomy, and those in the observation group were given laparoscopic cholecystectomy.The two groups were compared in terms of intraoperative and postoperative recovery (length of surgical incision, time of operation, intraoperative blood loss, time to postoperative ambulation, and length of hospital stay) , serum levels of LPS, AMY, and ACTH and immune function [T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+) ]before surgery and at 72 hours after surgery, and the incidence rate of complications after surgery.The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups.Results Compared with the control group, the observation group had significantly shorter length of surgical incision, time of operation, time to postoperative ambulation, and length of hospital stay, as well as significantly lower intraoperative blood loss (t = 26.782, 2.950, 11.559, 14.678, and 28.997, all P < 0.05) .The incidence of complications decreased during the 1-month follow-up (8.16% vs 22.45%, χ2= 9.137, P = 0.002) .There were no significant differences in the serum levels of LPS, AMY, and ACTH, the percentages of CD3+and CD4+T cells, and CD4+/CD8+ratio between the two groups before surgery (all P > 0.05) ; at 72 hours after surgery, compared with the control group, the observation group had significantly lower serum levels of LPS, AMY, and ACTH (t = 8.762, 5.370, and 3.607, all P < 0.001) and significantly higher percentages of CD3+and CD4+T cells and CD4+/CD8+ratio (t = 5.604, 6.611, and 12.025, all P < 0.001) .Conclusion Laparoscopic cholecystectomy has a good clinical effect in the treatment of AC and can effectively improve the serum levels of LPS and AMY, with a relatively slight impact on immune function.It helps to reduce postoperative stress response and incidence rate of complications.

Objective To investigate the clinical effect and safety of biliary metal stent implantation via endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of malignant extrahepatic biliary obstruction.Methods A total of 40 patients with unresectable malignant extrahepatic biliary obstruction who were admitted to The Second Affiliated Hospital of Zhengzhou University from January 2010 to December 2015 were enrolled, and according to the surgical method, these patients were divided into percutaneous transhepatic cholangiodrainage (PTCD) group and ERCP group, with 20 patients in each group.The two groups were compared in terms of duration of stent patency, survival time, postoperative clinical outcome, incidence of postoperative complications, and length of postoperative hospital stay.The t-test was used for comparison of continuous data between groups, and the chi-square test or the corrected chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to compare the differences in duration of stent patency and survival time between the two groups via the log-rank test.Results Compared with the PTCD group, the ERCP group had significant increases in duration of stent patency (225.6 ± 52.5 d vs 156.3 ± 44.5 d, t = 11.45, P < 0.05) and survival time (335.6 ± 42.5 d vs 225.5 ±42.5 d, t = 10.46, P < 0.05) .Seven patients in the ERCP group and 10 in the PTCD group experienced abdominal pain after surgery, and there was a significant difference between these two groups (35.0% vs 50.0%, χ2= 9.45, P < 0.05) .Compared with the PTCD group, the ERCP group had significantly lower incidence rate of severe postoperative complications (10.0% vs 30.0%, χ2= 7.49, P < 0.05) and shorter length of hospital stay (12.4 ± 2.5 d vs 19.8 ± 4.0 d, t = 10.67, P < 0.05) .Conclusion Metal stent implantation via ERCP has a similar clinical effect to PTCD in the treatment of malignant extrahepatic biliary obstruction, while compared with PTCD, ERCP allows for longer duration of stent patency and survival time, fewer complications, and a shorter length of hospital stay.Therefore, ERCP has better clinical effect and safety in patients with malignant extrahepatic biliary obstruction.

Objective To investigate the clinical effect and safety of minor endoscopic sphincterotomy (m EST) combined with endoscopic papillary large balloon dilation (EPLBD) in the treatment of elderly patients with multiple large common bile duct stones.Methods A retrospective analysis was performed for 229 patients with multiple large common bile duct stones who underwent endoscopic retrograde cholangiopancreatography (ERCP) in Endoscopy Center, Ankang Municipal Central Hospital, from January 2012 to December 2016, and the surgical procedure was selected based on the size of stones and the morphology of the common bile duct.According to the endoscopic surgical procedure, the patients were divided into m EST + EPLBD group (treatment group with 136 patients) and endoscopic phincterotomy (EST) group (control group with 93 patients) .The two groups were compared in terms of the success rate of first stone removal, use rate of mechanical lithotripsy (ML) , time spent on stone removal, and the incidence rate of complications.The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups.Results There was no significant difference in the success rate of first stone removal between the treatment group and the control group (91.17% vs 87.10%, χ2=0.980, P > 0.05) , while there were significant differences in the time spent on stone removal (18.2 ± 4.3 min vs 37.4 ± 6.7 min, χ2=37.1526, P < 0.01) and use rate of ML (6.71% vs 40.00%, t = 24.411, P < 0.01) .There were no significant differences in the incidence rates of pancreatitis (2.94% vs 6.45%, χ2= 1.630, P > 0.05) and bleeding (2.21% vs 2.15%, χ2= 0.001, P > 0.05) between the two groups, and no patient experienced perforation or infection.Conclusion m EST + EPLBD has a good clinical effect in the treatment of elderly patients with multiple large common bile duct stones and can effectively shorten the time spent on stone removal, reduce the use rate of ML, and thus reduce the recurrence rate of stones.In addition, this method does not increase post-ERCP complications and is a safe and effective therapeutic method for multiple large common bile duct stones in elderly patients.

Objective To investigate the predictive value of early measurement of serum inflammatory mediators for infectious pancreatic necrosis secondary to severe acute pancreatitis (SAP) .Methods A retrospective analysis was performed for the clinical data of 166 patients who were admitted to our hospital from January 2012 to January 2017.According to the presence or absence of secondary infectious pancreatic necrosis, the patients were divided into infection group with 58 patients and non-infection group with 108 patients.The serum levels of inflammatory factors were compared between the two groups.The receiver operating characteristic (ROC) curve was used for the analysis of indices with statistical significance.The independent samples t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups.Results Of all 166 SAP patients, 58 experienced secondary infectious pancreatic necrosis, resulting in an incidence rate of 34.9%.Compared with the non-infection group, the infection group had significantly higher serum lipase, procalcitonin (PCT) , C-reactive protein (CRP) , and APACHE II score (t = 8.679, 20.416, 18.429, and 8.563, all P < 0.05) .The ROC curve analysis showed that serum lipase, PCT, CRP, and APACHE II score had areas under the ROC curve of 0.647, 0.877, 0.823, and 0.655, respectively, with cut-off values of 612.5 U/L, 7.5 ng/ml, 226.5 mg/L, and 16.5 points, sensitivities of 68.5%, 91.2%, 86.8%, and 60.5%, and specificities of 59.3%, 83.6%, 80.1%, and 68.7%, respectively.Conclusion The abnormally elevated serum levels of CRP and PCT have a certain predictive value for infectious pancreatic necrosis secondary to SAP with convenient and fast operation, and therefore, it holds promise for clinical application.

Objective To investigate the effect of interference of Sema4D expression on cell biological behavior in pancreatic cancer.Methods Sema4D-siRNA was designed, synthesized, and transfected into a human pancreatic cancer cell line.The cells were divided into siRNA transfection group, negative control group (nonspecific transfection group) , and blank control group (untreated pancreatic cancer cells) .RT-q PCR was used to measure the change in the mRNA expression of Sema4D at 48 hours after transfection, and Western blot was used to measure the change in the protein expression of Sema4D at 72 hours after transfection.MTT assay was used to observe the change in cell growth after transfection, Transwell chamber invasion assay was used to observe the change in tumor cell invasion after transfection, and flow cytometry was used to observe the change in the apoptosis of tumor cells.An analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between any two groups.Results At 48 hours after Sema4D-siRNA transfection, the siRNA transfection group had significantly lower mRNA expression of Sema4D than the negative control group and the blank control group (F = 421.990, P < 0.001) .At 72 hours after Sema4D-siRNA transfection, the siRNA transfection group had significantly lower protein expression of Sema4D than the negative control group and the blank control group (F = 27.074, P =0.002 3) .At 48, 72, and 96 hours after transfection, the siRNA transfection group had a significantly lower cell growth rate than the negative control group and the blank control group (F = 15.314, 62.255, and 223.493, P = 0.004, < 0.001, and < 0.001) .The siRNA transfection group had a significantly lower number of cells which crossed the membrane than the negative control group and the blank control group (42.0 ± 5.9 vs 60.0 ± 6.1 vs 61.0 ± 4.6, F = 37.21, P = 0.000 4) .The siRNA transfection group had a significantly lower apoptosis rate than the negative control group and the blank control group [ (16.57 ± 0.31) % vs (9.50 ± 0.45) % vs (9.90 ± 0.61) %, F =26.75, P = 0.007 4].Conclusion Sema4D-siRNA can downregulate the expression of Sema4D in pancreatic cells and can inhibit the proliferation of pancreatic cancer cells and reduce their invasion ability and apoptosis.

Objective To investigate the clinical features of drug-induced liver injury (DILI) by descriptive analysis.Methods A retrospective analysis was performed for the clinical data of 445 patients who were diagnosed with DILI in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and Tongren Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to December 2016, including medical history, signs and symptoms, examination results, treatment, and prognosis.The clinical features of DILI were analyzed.The continuous data were expressed as median and inter-quartile range M (P25-P75) , and the Kruskal-Wallis H test was used for comparison of continuous data between groups; the chi-square test was used for comparison of categorical data between groups.Results Among all 445 patients, there were 136 male patients (30.56%) and 309 female patients (69.44%) , and most of the patients were aged 40-69 years.Of all patients, 194 (43.6%) had DILI induced by Western medicine, 140 (31.46%) had DILI induced by traditional Chinese medicine, 92 (20.67%) had DILI induced by Western medicine and traditional Chinese medicine, and 19 (4.27%) had DILI induced by healthcare products.Traditional Chinese medicine which induced DILI included Fallopia multiflora and its preparation, Xianling Gubao capsules, and Longbishu capsules, and Western medicine which induced DILI included cardiovascular drugs, antimicrobial agents, antipyretic and analgesic drugs, antitumor drugs, and antitubercular agents.Major clinical symptoms included weakness, poor appetite, jaundice, and nausea, among which weakness was the most common symptom, seen in 65.17% of all patients.Of all patients, 70.11% had hepatocellular injury type.There were significant differences in peak values of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , alkaline phosphatase, total bilirubin (TBil) , and international normalized ratio between patients with different types of DILI (t = 153.584, 97.366, 27.781, 24.177 and 6.236, all P < 0.05) , and the patients with liver injury induced by traditional Chinese medicine had significantly higher peak values of ALT, AST, and TBil than those with liver injury induced by Western medicine (all P < 0.05) .There was significant differences in liver injury score between patients with different types of DILI (χ2= 26.848, P < 0.001) .Of all patients, 98.65% achieved improvement, and there was no significant difference in prognosis between the patients with liver injury induced by traditional Chinese medicine and those with liver injury induced by Western medicine (χ2= 3.663, P > 0.05) .Conclusion DILI is commonly seen in female patients and middle-aged and elderly patients.Compared with those with liver injury induced by Western medicine, the patients with liver injury induced by traditional Chinese medicine have significantly greater abnormalities of biochemical parameters.Most of the patients with DILI have good prognosis.

Objective To investigate the role of chlorogenic acid (CG) in nonalcoholic fatty liver disease (NAFLD) and possible molecular basis, since NAFLD is closely associated with insulin resistance and CG can regulate glucose and lipid metabolism and improve insulin resistance.Methods A total of 30 Sprague-Dawley rats were randomly divided into normal diet group (NG group) , high-fat diet group (HG group) , and chlorogenic acid group (CG group) .All rats were given normal diet in week 1 as adaptive feeding; in weeks 2 and 3, the rats in NG group were given normal diet, and those in HG and CG groups were given high-fat diet; since week 4, the rats in NG and HG groups were given normal saline by gavage three times a week, and those in CG group were given CG by gavage three times a week.An automatic biochemical analyzer and radioimmunoassay were used to measure serum biochemical parameters, and a full-wavelength spectrophotometer was used to measure superoxide dismutase (SOD) , malondialdehyde (MDA) , and free fatty acid (FFA) .A euglycemic-hyperinsulinemic clamp was used to measure insulin resistance.Western blot was used to measure autophagy-related proteins and c-Jun N-terminal kinase (JNK) proteins.A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups.A Pearson correlation analysis was used for correlation analysis.Results Compared with the NG group, the HG group had significantly higher body weight, liver index, liver wet weight, alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , triglyceride (TG) , total cholesterol (TC) , tumor necrosis factor-α (TNF-α) , and levels of MDA and FFA in liver homogenate and a significantly lower level of SOD (all P < 0.05) .Compared with the NG group, the HG group had significant increases in the levels of p-JNK1 and JNK1 proteins and autophagy-related proteins LC3-Ⅰ, LC3-Ⅱ, Beclin-1, Atg3, and Atg5 (all P < 0.05) .The protein expression of JNK1 was positively correlated with insulin resistance.Compared with the HG group, the CG group had significantly lower body weight, liver wet weight, liver index, levels of ALT, AST, TG, TC, and TNF-α, and levels of MDA and FFA in liver homogenate, a significantly higher level of SOD, and significantly lower expression of LC3-Ⅰ, LC3-Ⅱ, Beclin-1, Atg3, and Atg5 (all P < 0.05) .Conclusion CG improves liver injury and insulin resistance by inhibiting autophagy via the inactivation of the JNK pathway.CG may be a potential method for the treatment of NAFLD.

Objective To evaluate the clinical features of patients with acute/subacute liver failure (ALF/SALF) complicated by acute kidney failure (AKI) .Methods A retrospective analysis was performed for the clinical data of 115 ALF/SALF patients who were admitted to302 Hospital of PLA from January 2015 to December 2016, and according to the presence or absence of AKI, these patients were divided into AKI group with 36 patients and non-AKI group with 79 patients.The two groups were compared in terms of age, sex, liver function, peripheral white blood cell count (WBC) , coagulation function, Model for End-Stage Liver Disease (MELD) score, and complications, and the prognosis of AKI patients was also observed.The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups.Results The most common cause of ALF/SALF was drug (49.57%) , followed by unknown causes (28.70%) .Of all 115 ALF/SALF patients, 36 had AKI, resulting in an incidence rate of31.3%, and the incidence rates of stage 1, 2, and 3 AKI were 11.30%, 14.78%, and 5.22%, respectively.Compared with the non-AKI group, the AKI group had significantly higher age, WBC, neutrophil ratio, incidence rates of ascites and abdominal/pulmonary infection, and MELD score (all P < 0.05) , as well as a significant reduction in the serum level of albumin (P < 0.05) .The AKI group had a significantly higher rate of no response/death than the non-AKI group (69.4% vs 38.0%, χ2= 9.815, P = 0.002) , and the mortality rate increased with the increase in the severity of AKI.Among the patients with stage 1, 2, and 3 AKI, 61.5%, 70.6%, and 83.3%, respectively, had no response or died.Conclusion Most of the patients with liver failure complicated by AKI have infections or inflammatory response, and the development of AKI is associated with the mortality of patients with liver failure.

Objective To investigate the effect of ulinastatin (UTI) preconditioning combined with ischemic preconditioning (IPC) on hepatic ischemia-reperfusion (IR) injury in rats and possible mechanism of action.Methods A total of 50 male Sprague-Dawley rats were randomly divided into sham-operation group, IR group, IPC group, UTI group, and UTI-IPC group (UCI group) .Blood samples were collected from the inferior vena cava after surgery and liver tissue samples were also collected.The serum levels of aspartate aminotransferase (AST) , alanine aminotransferase (ALT) , and tumor necrosis factor-α (TNF-α) , the levels of myeloperoxidase (MPO) and nuclear factor-kappa B (NF-κB) in the liver tissue, and wet/dry weight ratio were determined, and pathomorphological changes of the liver tissue were observed under a light microscope.A one-way analysis of variance was used for comparison of continuous data between groups, and the LSD-t-test was used for further comparison between two groups.Results The IR, IPC, UTI, and UCI groups had significantly higher serum levels of ALT, AST, and TNF-α, levels of MPO and NF-κB in the liver tissue, and wet/dry weight ratio than the sham-operation group (all P < 0.05) ; the IPC, UTI, and UCI groups had significantly lower levels than the IR group (all P < 0.05) , the UTI group had significantly lower levels than the IPC group (all P < 0.05) , and the UCI group had significantly lower levels than the IPC and UTI groups (all P < 0.05) .Liver pathological examination showed that compared with the sham-operation group, the IR, IPC, UTI, and UCI groups had significantly greater liver injury (all P < 0.05) , while the IPC, UTI, and UCI groups had a significantly lower degree of liver injury than the IR group (all P < 0.05) , the UTI group had significantly slighter liver injury than the IPC group (P < 0.05) , and the UCI group had significantly slighter liver injury than the IPC and UTI groups (both P < 0.05) .Conclusion Both UTI and UCI have a protective effect against hepatic IR injury, and the combination of UTI and UCI significantly enhances such protective effect, possibly by inhibiting the expression of NF-κB, reducing the release of TNF-α and MPO, and alleviating liver inflammatory response.

Objective To analyze whether Microtus fuscus in Qinghai-Tibet Plateau can be used as an animal model for Echinococcus infection.Methods Sixty wild voles (Microtus fuscus) were equally divided into groups A, B, and C to undergo Echinococcus inoculation through subcutaneous injection, direct transhepatic approach, and percutaneous transhepatic approach, respectively.Three months later, the infection rate and mortality rate were determined.After the model animals were sacrificed, HE staining was performed for the infiltration zone of lesion (2-3 mm near the lesion) , the area adjacent to the lesion and 50% of the lesion, the center of lesion (non-liquefied area) , the liquefied area of lesion, the margin of lesion (not including the normal tissue) , and 70% of the lesion, and the pathological structures of hydatid lesions were observed under a microscope.Protoscoleces were extracted from the lesions for in vitro culture.The chi-square test was used for comparison of categorical data.Results The success rate of Echinococcus infection in groups A, B, and C were 60%, 80%, and70%, respectively, with no significant difference between the three groups (χ2= 4.138, P = 0.126) .The mortality rates of groups A, B, and C were 5%, 20%, and 15%, respectively, with no significant difference between the three groups (χ2= 5.201, P = 0.107) .HE staining showed that the red-stained vesicles had thin, discontinuous cuticular layers, with massive inflammatory cell infiltration around the vesicles; no protoscoleces were observed in all sections.After in vitro culture and staining of the lesion tissue, a large number of live protoscoleces were observed, unstained and with motility.Conclusion This study confirms that Microtus fuscus, an endemic species in Qinghai-Tibet Plateau, can be used as an animal model for Echinococcus infection.Subcutaneous injection is an appropriate method for Echinococcus inoculation.

Hepatitis C virus (HCV) infection is a global public health issue.At present, pegylated interferon (IFN) combined with ribavirin is the major therapeutic regimen for anti-HCV treatment in China, but this regimen cannot achieve ideal sustained virologic response.Direct-acting antivirals (DAA) have achieved marked clinical effects in the treatment of patients with hepatitis C.This article briefly describes the change in immune status after anti-HCV treatment from the three aspects of innate immunity, adaptive immunity, and cytokines/chemokines.The analysis shows that HCV patients have complex immunoregulation, and the results vary from one study to another.In general, the expression of NK cell surface receptor and its function tend to recover and may even recover to a normal state.IFN treatment cannot restore the function of virus-specific CD8+T lymphocytes, while the change in cytotoxic T lymphocytes after DAA treatment has not been clarified.Further studies are needed to elucidate the long-term effect of DAA on cytokines and chemokines.

Chronic infection and inflammation are associated with the development of atherosclerosis, and hepatitis C virus (HCV) infection is a relatively common infectious disease.This article reviews the latest advances in the association between HCV infection and atherosclerotic diseases.Studies have shown that much evidence supports the fact that HCV infection can increase the incidence of coronary heart disease, stroke, and carotid atherosclerosis and the risk of death caused by cardiovascular events.HCV infection is a risk factor for atherosclerosis.Although the underlying mechanism needs further study, more attention should be paid to the prevention and control of atherosclerotic diseases among patients with hepatitis C.

Chronic hepatitis caused by hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma.In recent years, direct-acting antiviral agents (DAAs) have gradually become main drugs for the treatment of hepatitis C.Studies have shown that DAAs may increase the risk of the development or recurrence of liver cancer in patients with HCV-related liver cirrhosis, which causes great controversies over the clinical application of DAAs.This article reviews the influence of DAAs on the development and recurrence of liver cancer, in order to provide a better basis for the clinical application of DAAs.

Primary liver cancer ranks fourth among the common malignant tumors in China and is the third leading cause of death.At present, only 20% patients with liver cancer are eligible for radical resection.Many clinical studies have confirmed that transcatheter arterial chemoembolization (TACE) has a good effect in inhibiting tumor growth and recurrence and improving patients' survival rate and prognosis.This article reviews the indications for TACE in the treatment of primary liver cancer and its application in preoperative neoadjuvant therapy, postoperative adjuvant therapy, treatment of recurrence after liver cancer surgery, and bridging therapy before liver transplantation.

Primary liver cancer is a common malignant tumor in clinical practice, and secreted protein acidic and rich in cysteine (SPARC) plays a very important role in the progression and metastasis of liver cancer.This article introduces the structure and biological function of SPARC and analyzes its mechanism of action in malignant tumors and its association with the progression and metastasis of liver cancer, as well as the perspectives of its application in the diagnosis and treatment of liver cancer.

More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC) .With the development of science and technology, more and more targeted drugs have appeared.In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials.In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab.This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

The development and progression of hepatocellular carcinoma (HCC) is associated with estrogen, which exerts its physiological effect by binding to estrogen receptor (ER) .The function of ER is regulated by related genes, while the expression and function of these genes are affected by gene polymorphisms, and the genetic susceptibility to tumors is due to the combined effect of different genes and polymorphisms.Therefore, it is believed that ER gene polymorphisms may affect the development, progression, and prognosis of HCC.This article reviews the research advances in ER gene polymorphisms in recent years.

The incidence rate of nonalcoholic fatty liver disease (NAFLD) has been increasing year by year in China, and NAFLD has become one of the common chronic diseases that affect the health of Chinese residents.This article introduces the role of lifestyle intervention, reviews the types of drugs used in the treatment of NAFLD and their value, summarizes the methods and approaches for improving intestinal flora, and analyzes the clinical and economic benefits of surgical intervention in the treatment of NAFLD.It is pointed out that strengthening the effective management of patients with NAFLD may be a new research direction in the future for the treatment of this disease.

Acute liver failure (ALF) is a rare life-threatening disease with rapid progression and a low survival rate and affects the function of multiple organ systems.Early identification of cause and protection of vital organs are critical for patients' survival.With the development in artificial liver, stem cell transplantation, and liver transplantation in recent years, the outcome of ALF has been greatly improved.This article elaborates on the treatment of ALF from the aspects of the etiology of ALF and major organ systems involved and introduces the latest advances in artificial liver and stem cell transplantation.

Helicobacter pylori (HP) has been listed as the first carcinogen for gastric cancer by WHO.Recent studies have shown that HP infection is associated with a variety of tumors in other parts.This article introduces the current research on HP infection and intrahepatic/extrahepatic bile duct neoplasms from the aspects of classification and epidemiology of HP, association between HP and hepatobiliary tumors, and mechanism of tumorigenesis induced by HP, in order to provide a reference for further research on tumor etiology and diagnosis/treatment and improve the diagnosis/treatment and prognosis of cholangiocarcinoma caused by HP.