With reference to various clinical studies on interferon-α and pegylated interferon-α around the world,patients with chronic hepatitis C who receive antiviral therapy and achieve the elimination of hepatitis C virus may have significant relief or even reversion of liver fibrosis,as well as reductions in the incidence rates of decompensated liver cirrhosis,related complications,and hepatocellular carcinoma and an increase in survival rate.

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 IFNα and 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 expression of somatostatin receptors (SSTRs) in hepatocellular carcinoma (HCC) tissue and its association with clinicopathological features and prognosis of HCC.Methods HCC samples were collected from 80 patients who visited Third Hospital of PLA and Department of Hepatobiliary Surgery in The Second Affiliated Hospital of Dalian Medical University and who underwent hepatectomy from July 2012 to December 2014 and were diagnosed with HCC based on postoperative pathology (trial group).Another 80 patients who were suspected of liver disease and were not diagnosed with HCC by liver biopsy were enrolled as control group.RT-PCR and immunohistochemistry were used to measure the mRNA and protein expression of SSTR-2 and SSTR-3.The t-test was used for comparison of continuous data between groups,the chi-square test was used for comparison of categorical data between groups,the Kaplan-Meier method was used to analyze patients' survival,and the Cox regression analysis was used to investigate the influencing factors for the prognosis of HCC patients.Results The control group had significantly higher mRNA and protein expression of SSTR-2 and SSTR-3 than the trial group (t =6.456 and 8.128,x2 =7.992 and 9.157,all P ＜ 0.05).The univariate analysis showed that the mRNA expression of SSTR-2 and SSTR-3 was significantly correlated with tumor nodule (t =6.533 and 5.041,both P ＜ 0.05),degree of tumor differentiation (t =4.672 and 4.013,both P ＜ 0.05),depth of infiltration (t =6.735 and 7.019,both P ＜ 0.05),viral hepatitis (t =4.929 and 4.535,both P ＜ 0.05),alcoholic hepatitis (t =4.032 and 4.362,both P ＜ 0.05),and diabetes (t =4.372 and 6.293,both P ＜ 0.05),and the protein expression of SSTR-2 and SSTR-3 was significantly correlated with tumor nodule (x2 =25.223 and 15.399,both P ＜ 0.05),degree of tumor differentiation (x2 =7.535 and 10.944,both P ＜ 0.05),and depth of infiltration (x2 =22.520 and 9.968,both P ＜ 0.05).Compared with the group with positive expression of SSTR-2 and SSTR-3,the group with negative expression had significantly lower cumulative postoperative disease-free survival rate (P =0.015 and 0.004) and postoperative overall survival rate (P =0.009 and ＜ 0.001).The Cox model analysis showed that protein expression of SSTR-2 and SSTR-3,the number of tumor nodules,liver cirrhosis,and vein infiltration in HCC tissue were independent risk factors for overall survival after HCC surgery (P ＜ 0.05).Conclusion HCC patients have lower expression of SSTR-2 and SSTR-3 than non-HCC patients,and such low expression is closely associated with invasion/metastasis and poor prognosis of HCC.SSTRs may be the markers for the prognosis of HCC.

ObjectiveTo 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.