Hepatitis C virus infection is a global public health issue， and the emergence of direct-acting antiviral agents has brought revolutionary breakthroughs in the treatment of hepatitis C patients. Although direct-acting antiviral agents have a marked therapeutic effect in adult patients， there are still many challenges in the treatment of special populations such as pregnant women， infants， young children， and adolescents. This article reviews the current status of antiviral therapy for these special populations with hepatitis C and the problems that need to be solved， in order to provide reference and guidance for clinical workers.

Objective:To compare the real-world efficacy and safety profile of tenofovir amibufenamid (TMF) and tenofovir alafenamide (TAF) tablets in the treatment of patients with chronic hepatitis B (CHB).Methods:This retrospective study included patients with chronic hepatitis B who received TMF and TAF antiviral treatment at the Infectious Disease Outpatient Department of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023. The primary and secondary outcome was to study the patient HBV DNA conversion rate (<20 IU/ml), alanine aminotransferase (ALT) normalization rate, renal function, and lipid levels of patients at 48 weeks of treatment. The comparison of data between measurement data groups was differentiated using a t-test and Mann-Whitney U test. The inter-group comparison rate in count data was performed using the χ2 test or Fisher's exact probability. Results:A total of 440 cases were enrolled, including 220 in the TMF group (63 treatment-na?ve and 157 treatment-experienced) and 220 cases in the TAF group (61 treatment-na?ve and 159 treatment-experienced). In terms of efficacy, the HBV DNA seroconversion rates in the TMF group and TAF group were 90.5% and 85.2% ( P=0.372), respectively, while the ALT normalization rates were 92.1% and 88.5% ( P=0.505), respectively, at 48 weeks of treatment. The HBV DNA-negative conversion rate for the newly treated patients was 99.4% and 98.7%, respectively ( P=1.000), while the rates of ALT normalization were 94.9% and 92.3%, respectively ( P=0.863). In terms of safety profile, the serum creatinine level was lower in the TMF group than that in the TAF group at 48 weeks of treatment [TMF group 66.5 (56.3, 78.3) μmol/L, TAF group 70.6 (60.7, 77.8) μmol/L, Z=-2.282, P=0.022]. However, there was no statistically significant difference in other renal function and tubular function related indicators between the two groups of patients ( P>0.05). The serum high-density lipoprotein levels were higher in the TMF group than those in the TAF group [TMF 1.4 (1.1, 1.6) mmol/L vs. TAF group 1.3 (1.1, 1.6) mmol/L, Z=-2.204, P=0.027] at 48 weeks of treatment. However, there was no statistically significant difference in other blood lipid indicators between the two groups of patients ( P>0.05). Conclusion:There is no statistically significant difference in efficacy and safety profiles between TMF and TAF at 48 weeks in the treatment of patients with chronic hepatitis B, and the overall safety profile is favorable.

In 2022, Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association, organized domestic experts to update the guideline for the prevention and treatment of hepatitis C from the aspects of epidemiology, population screening and prevention, laboratory testing, simplification of diagnostic processes and treatment regimens, and antiviral therapy for special populations. This article aims to interpret the treatment of special populations not specifically mentioned in the new guideline, including pregnant women and patients with hepatocellular carcinoma, as well as other issues that need to be solved, in order to provide a reference for clinicians in practical work.

Objective:To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B.Methods:Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test.Results:A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance.Conclusion:Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log 10IU/ml), HBsAg level at 24 weeks (≤ 0.92 log 10IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log 10IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log 10IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.

Background:Zinc finger protein of cerebellum 2(ZIC2)is a transcriptional activator or repressor that is important for the organogenesis of the central nervous system.Previous studies have reported that ZIC2 is widely upregulated in a variety of tumors. Methods:Oncomine database was used to evaluate the expression levels of ZIC2 in hepatocellular car-cinoma(HCC)and normal liver tissues.Quantitative real-time polymerase chain reaction and immu-nohistochemistry were conducted to validate the results from the database.Cox regression analysis and survival curves were performed to assess the survival effect of ZIC2 in HCC. Results:Increased expression of ZIC2 was detected in HCC tissues compared with normal liver tissues.In addition,patients with high ZIC2 levels had a poor prognosis.Multivariate analysis showed that clinical stage(T or M classification)and ZIC2 levels were independent prognostic factors for overall survival.Moreover,a subgroup analysis revealed that patients with moderate or poor grade tumors,T1-2 tumors,N0 tumors,early American Joint Committee on Cancer(AJCC)stage,and old age were more likely to present with overexpression of ZIC2.To conclude,ZIC2 is upregulated in HCC and associated with the histology and survival of HCC patients. Conclusions:The expression status of ZIC2 may serve as an independent prognostic marker of HCC.

Objective:To observe the application value of virtual cognitive rehabilitation training in patients with mild cognitive impairment induced by transcatheter arterial chemoembolization (TACE) of liver neoplasms.Methods:By the convenience sampling method, a total of 126 liver neoplasms patients with mild cognitive impairment induced by TACE who were admitted and treated in the First Affiliated Hospital of Zhengzhou University from May 2015 to May 2019 were selected. They were randomly divided into the observation group and the control group, with 63 cases in each group. The control group was given routine cognitive intervention while the observation group was given virtual cognitive rehabilitation training, and the intervention lasted for 2 months. Montreal Cognitive Assessment Scale (MoCA) , Activities of Daily Living (ADL) Scale and Chinese version of Strategies Used by People to Promote Health (SUPPH) Scale were used to evaluate the cognitive function, ability of daily living and self-efficacy level of patients before and after intervention between two groups.Results:There was no statistically significant difference in MoCA, ADL, and SUPPH scale scores of patients between the two groups before the intervention ( P> 0.05) . After 2 months of intervention, the total score of the MoCA Scale (21.70 ± 5.27) and the total score of the SUPPH Scale (88.23 ± 21.43) in the observation group were higher than those in the control group, and the differences were statistically significant ( t=2.949, 4.509; P<0.05) . After intervention, the score of the ADL Scale in the observation group was (16.03±3.11) and that in the control group was (18.06±2.97) , and the difference was statistically significant ( t=3.747, P<0.05) . Conclusions:Virtual cognitive rehabilitation training can improve the cognitive function of liver neoplasms patients with mild cognitive impairment caused by TACE and improve the activity of daily living and self-efficacy.

Objective? To explore the effects of psychological flexibility intervention on the symptoms and self-management efficacy of patients after hepatic arterial infusion chemoembolization. Methods? By convenient sampling, a total of 90 patients with hepatocellular carcinoma who had undergone hepatic arterial transcatheter chemoembolization in the First Affiliated Hospital of Zhengzhou University from January to February 2018 were selected. By random number table method, they were divided into the observation group and the control group, with 45 participants in each group. The control group received routine nursing intervention, and the observation group received psychological flexibility intervention, both for 2 weeks. Before and after the intervention, the Memorial Symptom Assessment Scale (MSAS) and the Chinese version of the Strategies Used People to Promote Health (SUPPH) were used to assess the symptomatic distress and self-management efficacy of the two groups in order to evaluate the effects of the intervention. Results? There were no significant statistical differences in the average scores of physical symptoms, psychological symptoms, distressed index, and main clauses of MSAS before intervention between the two groups(P＞0.05). After intervention, the physical symptoms of the patients in both groups had no statistical difference compared with those pre-intervention (P＞0.05), while the average scores of psychological symptoms, distress index, main clauses of MSAS were all lower than those pre-intervention with statistical significance (P＜0.05). In the observation group, the average scores of psychological symptoms, distress index, and main clauses of MSAS were lower than the control group after intervention with statistical significance (P＜ 0.01). Before intervention, the total score of SUPPH and the score from each dimension in the scale between two groups had no statistical difference (P＞ 0.05). After intervention, the total score of SUPPH and the scores from each dimension increased with statistical significance (P＜0.05) while no statistical significance was found in the control group (P＞0.05). The total score of SUPPH and the scores from each dimension were all higher than the control group with statistical significance (P＜0.01). Conclusions? The psychological flexibility intervention can effectively reduce the patients' psychological distress after chemoembolization, and promote their self-management efficiency,therefore is worth promoting in the clinical practice.

In 2010,studies found that achievement of sustained virologic response after treatment in patients with chronic HCV infection meant cure;the overall cure rate of interferon combined with ribavirin around the world was about 60％,and the result of real-world study in China was 71.1％.In 2013,the US took the lead in launching the direct-acting antiviral agents (DAAs) for HCV,and the cure rate was increased to almost 100％.However,recent studies have found that the incidence of hepatocellular carcinoma (HCC) tends to increase after the application of DAAs,and there are still controversies over whether DAAs are the major cause of this phenomenon.In our opinion,this phenomenon is caused by the fact that the indications for DAAs cover more end-stage hepatitis C patients who are intrinsically the high-risk population of HCC;however,it cannot be excluded that DAAs may lead to the change in the body's antitumor immune status.Studies are needed in the future to examine this issue at the molecular level.

Objective To investigate the expression of PD-1 on CD4 +and CD8 + T cells in patients with HBeAg-positive chronic hepatitis B(CHB)treated with telbivudine.Methods Fifty-six HBeAg-positive CHB patients admitted in the First Affiliated Hospital of Zhengzhou University during January 201 3 and June 201 4 were enrolled in this study.The expression of PD-1 on CD4 +and CD8 + T cells was detected with flow cytometry at baseline,24,48 and 72 wks after telbivudine treatment.The relationship of PD-1 expression with alanine aminotransferase (ALT)level,HBeAg seroconversion and HBV DNA loads was analyzed.t test and completely random variance analysis were used to analyze the data.Results The PD-1 expression on CD4 + and CD8 + T cells at baseline was higher in patients with low ALT levels compared to those with high ALT levels(t =1 2.20 and 9.69,both P <0.01 ),while higher levels of PD-1 expression was also observed in patients with high HBV DNA load (≥5 lgIU /mL)compared to those with low HBV DNA load (t =4.39 and 4.85,both P <0.01 ).PD-1 levels on CD4 + and CD8 + T cells presented a declining trend after telbivudine treatment(F =6.98 and 8.97,both P <0.01 ),PD-1 expression in patients with HBeAg seroconversion showed lower levels compared with baseline values (t =1 8.45 and 1 8.01 ,both P <0.01 ). Conclusion In HBeAg-positive CHB patients,the expression of PD-1 on CD4 + and CD8 + T lymphocytes shows a decreasing trend during the treatment with telbivudine,indicating that antiviral therapy may alleviate the immunosuppression in these patients.

Objective To investigate the risk factors and predictive model for the occurrence of post-sustained virologic response (SVR)hepatocellular carcinoma in chronic hepatitis C (CHC)patients. Methods A total of 203 CHC patients hospitalized at the First Affiliated Hospital of Zhengzhou University from January 2006 to December 2014 who received antiviral therapy and achieved SVR were collected,including 11 post-SVR HCC cases.Risk factors for post-SVR HCC were estimated by Cox′s proportional hazards regression model.Cutoff value predicting risk of post-SVR HCC was determined by receiver operating characteristic curve.Results In Cox′s model,the risk of post-SVR HCC increased by 9.4-fold in patients with initial diagnosis as compensated cirrhosis compared to those with initial diagnosis as CHC.Increase in post-SVR albumin by per 1 g/L was associated with reduced risk by 20% for the occurrence of post-SVR HCC.Cut-off value of post-SVR albumin for the prediction of HCC was determined as ≤ 36.0 g/L with an area under the curve (AUC)of 0.809.A predictive model for post-SVR HCC was created based on initial diagnosis as compensated cirrhosis and post-SVR albumin ≤36.0 g/L with an AUC of 0.871 .The sensitivity,specificity and negative predictive value of the model were 0. 818,0.896 and 0.989,respectively.Conclusions Initial diagnosis as compensated cirrhosis combines with post-SVR albumin ≤36.0 g/L are risk factors for post-SVR HCC with ideal prediction value for the occurrence of post-SVR HCC in CHC patients.