Antiviral Therapy Group Research Articles

Preoperative Antiviral Therapy and Long-Term Outcomes for Hepatitis B Virus-Related Hepatocellular Carcinoma After Curative Liver Resection: A Multicenter Analysis.

To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing curative-intent hepatectomy. Patients who underwent curative-intent hepatectomy for HBV-related HCC between 2014 and 2019 at 4 Chinese hospitals were analyzed. Patients were categorized as having undergone preoperative antiviral therapy (AVT) > 1 year or without antiviral therapy (non-AVT). Patient clinical features, short-term outcomes, overall survival (OS), and time-to-recurrence (TTR) were also compared. Multivariate Cox regression analysis was performed to identify the impact of preoperative AVT on the OS and TTR. Among the 565 patients, 190 (33.6%) underwent continuous AVT > 1 year before surgery. Patients in the non-AVT group were more likely to have worse liver function and more advanced tumor pathological characteristics than those in the AVT group. Postoperative morbidity and mortality rates were comparable between the two groups. Multivariate analyses revealed that a preoperative HBV viral level ≥ 2000 IU/mL was independently associated with poorer TTR (hazard ratio, 1.328; 95% CI, 1.049-1.682) and preoperative AVT was a protective factor for OS (hazard ratio, 0.691; 95% CI, 0.484-0.986). A high preoperative HBV DNA level was an independent risk factor for tumor recurrence. Preoperative AVT > 1 year was associated with better OS and a reduced incidence of tumor recurrence by inhibiting the preoperative level of HBV DNA.

Abstract 12105: Cardioprotective Effect of Antiviral Therapy Among Hepatitis C Infected Patients: A Meta-Analysis

Background: Hepatitis C (HCV) infections have been shown to be associated with a higher risk of atherosclerotic cardiovascular disease (CVD). However, the use of antiviral therapy (AVT) and the risk of CVD has not been well established with limited literature. Objective: We sought to evaluate the association between AVT use post-HCV infection and cardiovascular outcomes. Methods: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10th March 2023. Primary clinical outcomes were the incidence of any CVD. Secondary endpoints were all-cause of mortality, stroke, myocardial infarction, peripheral artery disease, and heart failure. Results: A total of 394,452 patients were included in the analysis (111,076 in the AVT group and 283376 patients in the NAVT group). The mean age of patients among AVT and NAVT groups was comparable (58.7 vs. 58.18). The pooled analysis of primary outcomes showed that AVT was associated with a significantly reduced risk of any CVD (HR, 0.55(95%CI: 0.41-0.75), P<0.001) compared with the NAVT group of patients. Secondary outcomes including ACM (HR, 0.38(95%CI: 0.32-0.46), P<0.001), MI (HR, 0.62(95%CI: 0.41-0.94), P=0.02), and PAD (HR, 0.62(95%CI: 0.41-0.93), P=0.02) were significantly lower among AVT groups compared with NAVT groups of patients with HCV infection. However, the risk of stroke was comparable between both groups of patients (HR, 0.79(95%CI: 0.58-1.07), P=0.13). Conclusion: Our analysis shows HCV-infected patients post-AVT have a significantly lower risk of any CVD, MI, ACM, and PAD compared with NAVT groups of patients.

Cardioprotective effect of antiviral therapy among hepatitis C infected patients: A meta-analysis

BackgroundHepatitis C (HCV) infections have been shown to be associated a with higher risk of atherosclerotic cardiovascular disease (CVD). However, the use of antiviral therapy (AVT) and the risk of CVD has not been well established with limited literature. ObjectiveWe sought to evaluate the association between AVT use post-HCV infection and cardiovascular outcomes. MethodsWe performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10th March 2023. Primary clinical outcomes were the incidence of any CVD. Secondary endpoints were all-cause of mortality, stroke, myocardial infarction, and peripheral artery disease. ResultsA total of 394,452 patients were included in the analysis (111,076 in the AVT group and 283,376 patients in the NAVT group). The mean age of patients among AVT and NAVT groups was comparable (58.7 vs 58.18). The pooled analysis of primary outcomes showed that AVT was associated with a significantly reduced risk of any CVD (HR, 0.55(95%CI: 0.41–0.75), P < 0.001) compared with the NAVT group of patients. Secondary outcomes including ACM (HR, 0.38(95%CI: 0.32–0.46), P < 0.001), MI (HR, 0.62(95%CI: 0.41–0.94), P = 0.02), and PAD (HR, 0.62(95%CI: 0.41–0.93), P = 0.02) were significantly lower among AVT groups compared with NAVT groups of patients with HCV infection. However, the risk of stroke was comparable between both groups of patients (HR, 0.79(95%CI: 0.58–1.07), P = 0.13). ConclusionOur analysis shows HCV-infected patients post-AVT have a significantly lower risk of any CVD, MI, ACM, and PAD compared with NAVT groups of patients.

Clinicopathologic features and long-term prognosis of hepatitis B virus-associated glomerulonephritis: a retrospective cohort study

BackgroundHepatitis B virus-associated glomerulonephritis is a common form of secondary glomerulonephritis in China. However, the clinicopathological features and long-term prognosis of Hepatitis B virus-associated Glomerulonephritis remain only partially known.MethodsBiopsy-proven Hepatitis B virus-associated Glomerulonephritis patients were enrolled between November 1994 and December 2013 at our center. The composite endpoints were doubling serum creatinine, end-stage renal disease, or death from renal disease during follow-up. The clinicopathological features and predictors of the long-term prognosis of Hepatitis B virus-associated Glomerulonephritis patients were explored.ResultsThe median age of the 259 Hepatitis B virus-associated Glomerulonephritis patients was 31.0 years (IQR 24.0–40.0), and 71.0% were males. Among the patients, 45.2% presented with nephrotic syndrome, and 45.9% presented with proteinuria combined with hematuria. The two most prevalent pathological patterns were IgA nephropathy (27.0%) and membranous nephropathy (27.0%). The mean follow-up period was 68.8 ± 46.9 months. The 3-, 5-, and 10-year clinical event-free survival rates were 93.4%, 85.2%, and 70.3%, respectively. Multivariable Cox regression analysis showed that hypertension (HR 2.580, 95% CI 1.351–4.927, P = 0.004), hyperuricemia (HR 2.101, 95% CI 1.116–3.954, P = 0.021), glomerulosclerosis (P = 0.001), and intrarenal arterial lesions (P = 0.041) were independent predictors of composite clinical event endpoint. Patients in the antiviral therapy group exhibited a significantly better prognosis compared to those who received no antiviral therapy (log-rank χ2 = 5.772, P = 0.016).ConclusionHepatitis B virus-associated Glomerulonephritis has specific clinicopathologic features and should not be considered a benign disease in adults. Hypertension, hyperuricemia, glomerulosclerosis, and intrarenal arterial lesions were independent predictors of the long-term prognosis in Hepatitis B virus-associated Glomerulonephritis patients. Antiviral therapy could be effective in improving the long-term prognosis of Hepatitis B virus-associated Glomerulonephritis patients.Graphic abstract

Efficacy and Safety of Antiviral Therapy for Immune-tolerant Hepatitis B Viral Infection in Children: A Systematic Review and Meta-analysis.

Chronic hepatitis B virus (HBV) infection burden in children remains a pressing public health concern. Whether antiviral therapy should be administered to children with HBV in the immune-tolerant phase remains controversial. We performed a meta-analysis to evaluate antiviral therapy efficacy and safety in children with immune-tolerant hepatitis B (ITHB). A search was conducted in multiple databases (PubMed, Embase, Cochrane, Web of Science, CBM, CNKI and Wanfang Data) to identify clinical trials examining antiviral therapy efficacy and safety in children (1-18 years) with ITHB viral infection from inception to February 2023. Outcomes were calculated separately for controlled and single-arm studies. Nine trials (442 patients), including 2 randomized controlled trials (RCTs), 3 non-RCTs and 4 single-arm studies, were included in this meta-analysis. In the RCTs, antiviral therapy group exhibited greater rates of HBsAg loss [risk ratio (RR) = 6.11, 95% confidence interval (CI): 1.67-22.31, P Z-test = 0.006], HBsAg serologic response (RR = 5.29, 95% CI: 1.47-19.07, P Z-test = 0.011) and HBeAg loss (RR = 3.00, 95% CI: 1.35-6.66, P Z-test = 0.007) compared with the control group at the end of follow-up. In single-arm studies, the pooled incidences of HBsAg loss, HBeAg loss and HBsAg seroconversion were 24% (95% CI: -0.1% to 48%), 24% (95% CI: -0.1% to 48%) and 24% (95% CI: -5% to 52%), respectively. Current evidence suggests the effectiveness of antiviral therapy in children with HBV infection in the immune-tolerant stage, with few serious adverse events. Due to the limited quality and number of included studies, more high-quality studies are required to validate our findings.

The impact of HCV chronic positivity and clearance on extrahepatic morbidity in thalassemia major patients: an observational study from MIOT Network

BackgroundNo study has evaluated the effect of hepatitis C virus (HCV) infection on the wide spectrum of complications affecting patients with thalassemia. ObjectivesThis multicenter study prospectively assessed the relationship of HCV infection with diabetes mellitus and cardiovascular complications in patients with thalassemia major (TM). MethodsWe considered 1057 TM patients (539 females; 29.79±10.08 years) enrolled in the MIOT Network and categorized into 4 groups: negative patients (group 1a, N=460), patients who spontaneously cleared the virus within 6months (group 1b, N=242), patients who eradicated the virus after the treatment with antiviral therapy (group 2, N=102), and patients with chronic HCV infection (group 3, N=254). ResultsGroup 1a and 1b were considered as a unique group (group 1). For both groups 1 and 3, a match 1:1 for age and sex with group 2 was performed. The effective study cohort consisted of 306 patients (three groups of 102 patients).During a mean follow-up of 67.93±39.20months, the group 3 experienced a significantly higher % increase/month in aspartate transaminase levels and left ventricular mass index than both groups 1 and 2. The changes in iron overload indexes were comparable among the three groups.Compared to group 1, the chronic HCV group showed a significantly higher risk of diabetes (hazard ratio-HR=5.33; p=0.043) and of cardiovascular diseases (HR=3.80; p=0.034). ConclusionChronic HCV infection is associated with a significant higher risk of diabetes mellitus and cardiovascular complications in TM patients and should be approached as a systemic disease in which extrahepatic complications increase the weight of its pathological burden.

Antiviral therapy inhibited HBV-reactivation and improved long-term outcomes in patients who underwent radiofrequency ablation for HBV-related hepatocellular carcinoma

BackgroundHepatitis B virus (HBV) reactivation impact negatively the prognosis of patients with HBV-related hepatocellular carcinoma (HCC). This study aimed to observe the effect of antiviral therapy (AVT) on viral reactivation and long-term outcomes after percutaneous radiofrequency ablation (PRFA) for HBV-related HCC.MethodsData on 538 patients between 2009 and 2013 were reviewed. Propensity score matching (PSM) analysis was used to adjust for differences in baseline features between patients who received AVT (AVT group) and did not receive it (non-AVT group). Logistic regression was used to identify the independent factors for viral reactivation. The tumor recurrence and overall survival (OS) rates were analyzed using the Kaplan–Meier method. Recurrence patterns were also investigated.ResultsHBV reactivation developed in 10.8% (58/538) of patients after PRFA. AVT was associated independently with decreased viral reactivation (odd ratio: 0.061, 95% confidence interval: 0.018–0.200). In 215 pairs of patients obtained after PSM, the AVT group had lower 1-, 3-, and 5-year recurrence rates (24%, 55%, and 67% vs 33%, 75%, and 85%, respectively) and higher 1-, 3-, and 5-year OS rates (100%, 67%, and 59% vs 100%, 52%, and 42%, respectively) than non-AVT group (P < 0.001 for both). Additionally, the relapses in distant hepatic segments and the late recurrence after 2 years of PRFA were significantly reduced in the AVT group (78/215 vs 111/215 vs., P = 0.001; 39/109 vs. 61/91, P = 0.012, respectively).ConclusionsAVT reduced late and distal intrahepatic recurrence and improved OS in patients undergoing PRFA for HBV-related HCC by inhibiting viral reactivation.

Efficacy of Adjuvant Transarterial Chemoembolization Combined Antiviral Therapy for HBV-Related HCC with MVI after Hepatic Resection: A Multicenter Study.

Efficacy of transarterial chemoembolization (TACE) combined antiviral therapy (AVT) on long-term outcome in hepatitis B virus-related HCC with microvascular invasion (MVI) after hepatic resection is unclear. A multicenter retrospective study was conducted. All patients were divided into four groups according to postoperative adjuvant therapy (control group, AVT group, TACE group, and combined group). The overall survival (OS) and recurrence-free survival (RFS) were analyzed. A total of 1090 patients were enrolled in this study, including control group (n=319), TACE group (n=152), AVT group (n=335) and combined group (n=284). Multivariate Cox analysis showed that postoperative adjuvant AVT and TACE were the independent protective factors for OS and RFS. The median OS among the control group, TACE group, AVT group, and the combined group were 16.44, 18.36 months, 38.88 months, and 48.24 months respectively(p<0.01). The median RFS among 4 group were 4.68, 5.40 months, 8.64 months and 10.32 months respectively(p<0.01). Postoperative adjuvant TACE and AVT were the independent protective factors associated with mortality and tumor recurrence in HBV-related HCC with MVI after resection. This combined treatment strategy may provide useful clinical significance in the prevention of tumor recurrence in these patients.

Antiviral therapy improves postoperative survival of patients with HBV-related hepatocellular carcinoma

BackgroundWe aimed to investigate whether improvements in the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who have undergone hepatectomy are associated with reductions in the liver inflammation and fibrosis by antiviral therapy (AVT). MethodsPatients who underwent hepatectomy and re-hepatectomy for HBV-related HCC between 2010 and 2019 were divided into two groups. Histological changes in liver were compared between initial and recurrence stages within each group. Propensity score matching (PSM) analysis was performed to compare prognostic outcomes. ResultsAfter PSM, AVT group showed a significantly better prognosis than did non-AVT group (RFS: 19.1% vs. 5.8%, P = 0.001; OS: 64.0% vs. 43.2%, P < 0.001). The improvements in G and S were independent protective factors for RFS (G: P < 0.001; S: P < 0.001) and OS (G: P = 0.013; S: P < 0.001). ConclusionsThe application of AVT after initial surgery improved liver inflammation and fibrosis, further benefiting long-term outcomes of patients with HBV-related HCC.

Safety and Efficacy of Antiviral Therapy for Chronic Hepatitis B Throughout Entire Pregnancy

Background: The data of antiviral therapy throughout the entire pregnancy are relatively scarce. The aim of the present study was to evaluate the safety and efficacy of antiviral therapy for chronic HBV infection throughout the entire pregnancy.Methods: This was a single-center, prospectively study. Fifty-five women received antiviral therapy (TDF or LDT) from pre-conception to the entire pregnancy. Sixty-four women did not receive antiviral therapy during pre-conception and the entire pregnancy. All infants in the two groups had received immunoprophylaxis on schedule. Mother-infant pairs were followed up at least 7 months postpartum. The outcome was the safety and efficacy of antiviral therapy for mothers and offspring.Findings: All mothers tolerated antiviral therapy (TDF or LDT) well. The mean maternal HBV DNA level in the antiviral therapy group was less than that of the control group before delivery as well as in the three months postpartum (PP=0.010). However, in 3 months postpartum, there was not a statistically significant difference in the maternal serum ALT level between the two groups (P=0.185). There was not a statistically significant difference in the pregnancy complications, the gestational weeks, and the mode of delivery between the two groups, respectively (P>0.05). Furthermore, there was not a statistically significant difference in the birth weight, the birth length, and the congenital diseases of infants between the two groups, respectively (P>0.05). In 7 months postpartum, none of infants who tested HBV status in the two groups was positive for HBsAg.Interpretation: Antiviral therapy (TDF or LDT) from pre-conception to the entire pregnancy could be safe and effective for pregnant women with HBV infection and their fetuses/ infants.Trial Registration: The present study was registered in ClinicalTrials.gov (No. NCT03181607).Funding Statement: The present study was funded by the National Key Research and Development Program of China (2017YFC1001402, 2018YFC1002900), National Natural Science Foundation of China (81401306, 81830045), Clinical Research Project of Guangzhou Medical University (No. 2017[160]) and Sino-German Center for Research Promotion (SGC)'s Rapid Response Funding Call for Bilateral Collaborative Proposals between China and Germany in COVID-19 Related Research (No. C-0032).Declaration of Interests: All authors declare no financial, potential personal or commercial conflict of interest.Ethics Approval Statement: The present study was approved by the Institutional Ethics Committee of the Third Affiliated Hospital of Guangzhou Medical University, and was carried out in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed written consent was obtained from each participant in the present study.

Peginterferon Alfa-2a (40KD) Plus Lamivudine or Entecavir in Children With Immune-Tolerant Chronic Hepatitis B.

Treatment guidelines for chronic hepatitis B (CHB) do not recommend antiviral therapy for patients in the immune-tolerant phase of the disease, which generally occurs in children who acquire hepatitis B virus (HBV) vertically and may last for decades. On the basis of promising results of a pilot study, we conducted a randomized, controlled, multicenter study to evaluate the efficacy and safety of antiviral therapy in children and adolescents with immune-tolerant CHB. Fifty-nine children aged 3 to <18 years hepatitis B e antigen-positive with an HBV DNA titer >20,000 IU/mL and persistently normal alanine aminotransferase levels were randomized to 56 weeks of antiviral therapy with an oral nucleoside analogue [entecavir or lamivudine], combined with subcutaneous peginterferon alfa-2a from week 8, or 80 weeks of untreated observation. The primary efficacy outcome was hepatitis B surface antigen loss 24 weeks post-treatment in the antiviral therapy group or at the end of observation in the control group. Enrollment was terminated after the results of two similar studies showed that similar antiviral regimens were ineffective in children and adults with immune-tolerant CHB. At 24 weeks post-treatment, 1 of 26 patients in the antiviral treatment group experienced HBsAg loss (vs none of 33 patients in the control group). No serious treatment-related adverse events were reported, and no patients discontinued treatment because of adverse events. The antiviral regimen evaluated in this trial had an acceptable tolerability profile, but was ineffective in children and adolescents with immune-tolerant CHB.

Association between liver fibrosis and appendicular skeletal muscle mass during antiviral therapy in chronic hepatitis B

Background and aimsSarcopenia is associated with fibrotic burden in patients with chronic hepatitis B. We investigated the dynamic association between fibrosis changes and appendicular skeletal muscle mass during antiviral therapy in patients with chronic hepatitis B. MethodsBetween 2015 and 2018, chronic hepatitis B patients who received paired transient elastography to assess fibrotic burden in the liver and bioelectrical impedance analysis to assess appendicular skeletal muscle mass were recruited retrospectively. The sarcopenia index was calculated as total appendicular skeletal muscle mass/body mass index. Significant liver fibrosis was defined as a liver stiffness value≥8 kPa. ResultsIn total, 223 (53.7%) received antiviral therapy, whereas 192 (46.3%) did not. Appendicular skeletal muscle mass decreased significantly in the antiviral therapy group (mean 21.16→21.00 kg, P = 0.01), but not in the non-antiviral therapy group (mean 20.77→20.64 kg, P = 0.134). In a subgroup with significant liver fibrosis, similar findings were observed (mean 20.73→20.54 kg in antiviral therapy group, P = 0.037; mean 21.39→21.07 kg in the non-antiviral therapy group, P = 0.097). Older age, male gender, higher body mass index, and higher aspartate aminotransferase were significantly associated with the increased risk of appendicular skeletal muscle mass reduction (≥5% from the baseline). ConclusionsAppendicular skeletal muscle mass significantly decreased during antiviral therapy in patients with chronic hepatitis B patients.

Perioperative antiviral therapy improves the prognosis of HBV DNA-negative patients with HBV-related hepatocellular carcinoma

ABSTRACT Objective To investigate the effect of perioperative antiviral therapy on the prognosis of hepatitis B virus (HBV) DNA-negative patients with HBV-related hepatocellular carcinoma (HCC). Methods The clinical data of 140 patients who were positive for hepatitis B surface antigen (HBsAg) but negative for HBV DNA before partial hepatectomy were retrospectively analyzed. Propensity score matching (PSM) was used to eliminate the influence of confounding factors on prognosis. Postoperative liver function, HBV reactivation rate, recurrence-free survival (RFS) and overall survival (OS) were compared between antiviral and non-antiviral therapy groups. Results Compared with the non-antiviral therapy group, the antiviral therapy group had a lower rate of HBV reactivation and better postoperative liver function (P < 0.05). The 1-year, 2-year and 3-year survival rates of the antiviral therapy group were better than those of the non-antiviral therapy group before or after PSM (P < 0.05). Prognostic analysis excluding 11 patients with HBV reactivation showed that perioperative antiviral therapy could significantly improve OS (P = 0.004), but had no significant effect on RFS (P = 0.056). Multivariate analyzes showed that antiviral therapy was associated with better OS. Conclusion Perioperative antiviral therapy can significantly reduce the risk of HBV reactivation and improve postoperative liver function, RFS and OS.

Serum Hepcidin In Patients With Chronic Hepatitis C And Its Relation To Treatment With Antiviral Drugs

HCV infection has been implicated in iron accumulation in the liver and iron overload has been shown to be a potential cofactor for HCVassociated hepatocellular carcinoma progression.Hepcidin produced by hepatocytes, is a key regulator of iron metabolism. Alteration of Hepcidin expression levels has been reported in the setting of chronic HCV infection and hepatocellular carcinoma. The aim of the work is to assess the serum concentration of hepcidin in chronic hepatitis C patients and evaluate any possible association with the viral load after therapy. Ourstudy was carried on50 patients with chronic hepatitisC.Hepcidin levels were evaluated for Hepcidin before starting the antiviral therapy treatment (group A) and after 24 weeks course of antiviral therapy(group B)with a commercially available enzyme-linked immunosorbentassay kitin addition to 20 healthy volunteers with matched age and sex as control group.As regard serum Hepcidin level, there was a highly statistical significant differencebetween control and patient group.Hepcidin concentrations in patients with CHC were relatively low compared to HCV negative individuals. Highly statistical significant (p-value > 0.05) positive correlation (r = 0.67) between Hepcidin before and after treatment in patients group. In conclusion Chronic HCV infection is associated with reduced level of hepcidin. The level of hepcidin was fully reversible after antiviral therapy.Initial rise in serum hepcidin concentration might have a potential for being used as one of the indicators of patient response to therapy.

Association of Prophylactic Anti-Hepatitis B Virus Therapy With Improved Long-term Survival in Patients With Hepatocellular Carcinoma Undergoing Transarterial Therapy.

The effect of prophylactic antiviral therapy (AVT) on survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine whether prophylactic AVT could improve long-term survival in patients undergoing transarterial chemotherapy (TAC). Between 2002 and 2016, 2860 newly diagnosed HBV-related patients with HCC treated with TAC were screened to analyze 2 groups based on prophylactic use of antivirals. Treatment effects were analyzed using propensity score (PS) matching (1:1) separately for the entire cohort and each subgroup. The primary endpoint was overall survival. A total of 1547 patients met the inclusion criteria and 1084 were PS matched for the 2 groups. Median follow-up duration was 16.55 months. In the entire unmatched cohort, patients receiving prophylactic AVT survived significantly longer than those who did not. Among AVT-untreated patients, baseline high viremia and HBV reactivation during treatment were significantly associated with shorter survival. Regarding types of antivirals, survival was significantly longer for patients receiving high-potency antivirals than those receiving low-potency antivirals. Survival differed with antiviral response. In the PS-matched cohort, the prophylactic AVT group survived significantly longer than the nonprophylactic group, irrespective of viral status or tumor stage. Prophylactic AVT remained an independent factor for survival. The association of prophylactic AVT with decreased risk of mortality persisted in patient subgroups after adjusting for baseline risk factors. Sensitivity analyses also confirmed estimated treatment effects. Prophylactic AVT is associated with significantly improved long-term survival among patients undergoing TAC. High-potency antivirals are indicated for this approach.Hepatitis B virus-associated morbidity is a well-known complication during transarterial chemotherapy (TAC). Our large-scale study demonstrated that prophylactic therapy with high-potency antivirals provides a significantly better survival in TAC-treated patients, irrespective of baseline viremia status or tumor stage.

Antiviral therapy predicts the outcomes following resection of hepatocellular carcinoma in patients negative for HBV DNA: a propensity score matching analysis

BackgroundThe effect of antiviral therapy (AVT) on clinical outcomes in patients with hepatocellular carcinoma (HCC) who are seronegative for hepatitis B virus (HBV), defined as HBV DNA < 100 IU/ml prior to surgical resection, is unknown. The main purpose of this study was to evaluate the possible value of AVT in this cohort of patients.MethodsFrom January 2006 to January 2013, 161 HCC patients with positive serum tests for HBV surface antigen (HBsAg) but negative tests for HBV DNA who had undergone hepatectomy were included and analyzed. Propensity score matching (PSM) was used to balance the heterogeneity in baseline characteristics.ResultsAll patients were divided into the following two groups: the AVT group (n = 73, 45.34%) and the non-AVT group (n = 88, 54.66%). HBV reactivation occurred in 20 patients in the non-AVT group (22.73%) but in only 2 patients in the AVT group (2.74%, p < 0.001). After PSM, the 1-, 2-, and 3-year recurrence-free survival (RFS) rates in the AVT group and the non-AVT group were 78.38%, 72.97%, and 62.16% and 81.08%, 72.97%, and 72.97%, respectively (p = 0.564); the 1-, 2-, and 3-year overall survival (OS) rates were 97.30%, 97.3%, and 91.89% and 94.59%, 94.59%, and 86.49% in the AVT group and non-AVT group, respectively (p = 0.447).ConclusionsAntiviral therapy can reduce HBV reactivation but is not correlated with a significant increase in postoperative RFS and OS in HCC patients with HBV DNA levels < 100 IU/ml.

Adjuvant therapy of cytomegalovirus IgM + ve associated biliary atresia: Prima facie evidence of effect

Aim of studyCMV-IgM + ve associated biliary atresia (CMV-BA) is a distinct etiological subgroup characterized by older age at presentation and a greater degree of inflammation and hepatic fibrosis, leading to a worse outcome. We report our experience with adjuvant antiviral therapy after Kasai portoenterostomy (KPE). MethodsSingle-center prospective database identification of CMV-IgM + ve associated BA managed between 2003 and 2017. Since 2011, IV ganciclovir (5 mg/kg b.d.) and/or oral valganciclovir (520 mg/m2 b.d.) were started in the early postoperative period in selected cases and continued until negativity of CMV DNA load [Anti-Viral Therapy (AVT) Group 1]. Clearance of jaundice was defined as achieving a total bilirubin ≤20 μmol/L in post-KPE period and tested with a Fisher test; native liver survival (NLS) and overall actuarial survival (OS) were compared with untreated BA CMV IgM + ve patients (Group 2) using a Log-Rank test. A P value of <0.05 was regarded as significant. Data are quoted as median (IQ range). ResultsDuring the 14-year period, 376 infants with histologically confirmed BA were treated; of those 38(10%) were CMV IgM + ve at presentation. One child was considered too late at presentation for KPE and underwent primary liver transplantation while another only started AVT one month after KPE. Both were excluded from survival analysis. Therefore 36 underwent KPE [AVT Group 1 (n = 8) and Control Group 2 (n = 28)]. Overall age at surgery was 67(53–77) days. There was no difference in age at surgery (P = 0.26); bilirubin (P = 0.12); or AST (P = 0.15) between Group 1 and Group 2. Viral load data were available in 16 with a trend towards higher counts in the AVT group 1 [4935 (2668–18,817) vs. 1296 (253–10,471) c/ml; P = 0.06]. Clearance of jaundice was higher in AVT Group 1 (75% vs 21%, P = 0.009). There was no difference in OS (P = 0.24) but NLS was improved in the AVT Group 1 (75% vs. 25% at 2 years; P = 0.04). ConclusionsAlthough this finding may be regarded as preliminary, adjuvant antiviral therapy appeared to improve outcome in infants with CMV IgM + ve BA. Level of evidenceIII.

Corticosteroid therapy in pneumonia from swine-origin influenza A (H1N1) in China.

The first three cases of confirmed infection with the virus in China were documented between May 10 and May 15, 2009. Although the clinical characteristics of the H1N1 pneumonia were described in clinical reports, the therapy has few been described. Therefore, we report our experiences of 53 cases of the H1N1 pneumonia with treatment. We describe clinical characteristic of 53 patients who were hospitalized for laboratory-confirmed H1N1 pneumonia at the 2nd Clinical College of Harbin Medical University. In addition, we measure the role of corticosteroid, mechanical ventilation, and non-corticosteroid antiviral therapy in the management of pneumonia patients with novel H1N1 infection. Real-time reverse-transcriptase-polymerase chain (RT-PCR) testing was used to confirm infection. The outcome of therapy was compared in scores of PaO2 and CT. The data was statistical analyzed by the Shapiro-Wilk, anova, Student-Newman-Keuls Test, and Kruskal-Wallis Test. The most common symptoms were dyspnea. In moderate ill patients, the changes in the increased PaO2 were lower in the non-corticosteroid antiviral therapy group than in the combination of corticosteroid and non-corticosteroid antiviral therapy after 5 days' therapy. The therapy protocol of non-corticosteriod + mechanical ventilation played important role in the recovery of severe ill patients.

Changes of hepatitis B core antigen-specific cytotoxic T lymphocytes in chronic hepatitis B patients during antiviral treatment and relapse after withdrawal of treatment

Objective To explore the potential mechanism of severe liver injury shortly after withdrawal of antiviral therapy in chronic hepatitis B (CHB) patients. Methods Forty-nine patients with chronic hepatitis B virus (HBV) infection from the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University and 8 healthy volunteers from August 2014 to March 2015 were included in this study. All of them were human leukocyte antigen (HLA)-A2-positive. CHB patients were classified into three groups, including 15 cases in immune-tolerance group, 20 cases in sustained antiviral treatment group, and 14 cases in recurrence of drug withdrawal group. The frequency of peripheral HLA-A0201-restricted hepatitis B core antigen (HBcAg)18-27 pentamer complex specific CD8+ T cells in CHB patients was analyzed by flow cytometry. Enzyme linked immunospot assay(ELISPOT) was used to detect interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) secretions of HBcAg18-27-specific CD8+ T cells. The experimental data were analyzed using non-parametric U tests. Results In healthy control group, immune-tolerance group, sustained antiviral treatment group and recurrence of drug withdrawal group, the frequencies of HBcAg-specific CD8+ T cells were (0.17±0.16)%, (1.46±0.72)%, (3.24±1.60)% and (4.67±2.43)%, respectively. Compared with healthy control group, the difference were all statistically significant in the three groups (Z=-3.583, -4.018 and -3.823, respectively; all P<0.01). The frequencies of HBcAg-specific CD8+ T cells in immune-tolerance group or recurrence of drug withdrawal group were both significantly different from that in sustained antiviral therapy group (Z=-3.400 and -2.030, respectively; both P<0.05). The difference between immune-tolerance group and recurrence of drug withdrawal group was also significant (Z=-3.230, P<0.01). The secretion levels of IFN-γ of HBcAg-specific CD8+ T cells in healthy control group, immune-tolerance group, sustained antiviral treatment group and recurrence of drug withdrawal group were 2 (0-6), 16 (2-53), 106 (14-254) and 156 (28-395) spot forming cell (SFC)/106 peripheral blood mononuclear cell (PBMC), respectively. The differences between healthy control group and immune-tolerance group, sustained antiviral treatment group or recurrence of drug withdrawal group were all statistically significant (Z=-3.585, -4.069 and -3.824, respectively; all P<0.01). The IFN-γ level of HBcAg-specific CD8+ T cells in recurrence of drug withdrawal group was significantly higher than that in sustained antiviral therapy group (Z=-2.205, P=0.027), and that in sustained antiviral therapy group was significantly higher than that in immune-tolerance group (Z=-4.700, P<0.01). The TNF-α levels secreted by HBcAg-specific CD8+ T cells in each group were 2 (0—5), 16 (2—32), 112 (15—283), and 195 (55—537) SFC/106 PBMC, respectively. The differences between healthy control group and immune-tolerance group, sustained antiviral treament group or recurrence of drug withdrawal group were all statistically significant (Z=-3.619, -4.069 and -3.824, respectively; all P<0.01). The TNF-α level secreted by HBcAg-specific CD8+ T cells in recurrence of drug withdrawal group was significantly higher than that in sustained antiviral therapy group (Z=-2.449, P=0.014), and that in sustained antiviral therapy group was significantly higher than that in immune-tolerance group (Z=-4.350, P<0.01). Conclusions The changes of frequency and immune function of HBcAg-specific CD8+ T cells in CHB patients may be one of the reasons causing severe liver damage after irregular withdrawal of nucleoside analogues. Key words: Hepatitis B; T-lymphocytes, cytotoxic; Antiviral treatment; Recurrence

소라페닙 투여 간세포암종 환자에서 항바이러스제 치료의 생존이득

Background/Aims: Nucleos(t)ide analogues (NAs) help reduce the recurrence rate after the curative treatment of hepatitis B related hepatocellular carcinoma (HCC). Sorafenib has been shown to improve survival of advanced HCC patients. Whether antiviral therapy with NAs could help such patients is unknown. Our aim is to investigate the usefulness of antiviral therapy for advanced-stage HCC treated with sorafenib. MethodsWe performed a retrospective cohort study in advanced-stage HCC patients treated with sorafenib between June 2007 and December 2013. Patients in group A (the nonantiviral therapy group) were treated with sorafenib alone. Those in group B (the antiviral therapy group) were treated with sorafenib and NAs. Progression-free survival (PS) and overall survival (OS) were compared between these two groups. ResultsFinally, 23 patients in group A and 40 patients in group B were enrolled in the study. The mean number of days of treatment with sorafenib was 79 (34-231) days and 96 (33-449) days for group A and B, respectively (P=0.286). The mean PS of group A and B was 97 (14-449) days and 51 (0-461) days, respectively (P=0.068). The OS was 154 (44-741) days in group A and 138 (30-1,025) days in group B (P=0.665). PS and OS showed no significant difference between the two groups. ConclusionsThis study shows that there was no significant survival gain of using antiviral therapy in patients with advanced-stage HCC treated with sorafenib. In consideration of costeffectiveness, antiviral therapy may be not mandatory. (J Liver Cancer 2016;16:23-30)