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临床与转化肝病杂志（英文版）
临床与转化肝病杂志（英文版）

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临床与转化肝病杂志（英文版）/Journal Journal of Clinical and Translational Hepatology
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    Unraveling the Dynamic Role of Microtubules in the HBV Life Cycle

    Urania GeorgopoulouJohn Koskinas
    383-385页
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Acute Severe Hepatitis of Unknown Origin in Children Across the World: A 2022 Source of Concern

    Lampros ChrysavgisEvangelos Cholongitas
    386-389页
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Change of Cytokines in Chronic Hepatitis B Patients and HBeAg are Positively Correlated with HBV RNA, Based on Real-world Study

    Qiqi ZhangHui HuangAijun SunChunyan Liu...
    390-397页
    查看更多>>摘要：Background and Aims: The natural course of chronic hep-atitis B virus (HBV) infection is widely studied; however, follow-up studies of the same patients are scanty. Here, we studied the dynamic changes of serum HBV RNA and cytokines in hepatitis B virus e antigen (HBeAg)-positive patients treated with entecavir (ETV) to explore the rela-tionship between the HBV serum viral nucleic acids and host immunity. Methods: Thirty-three chronic hepatitis B patients who are HBeAg-positive, with high virus load (HBV DNA >20,000 IU/mL), and received standard nucleos(t) ide analogue (NA) antiviral therapy (ETV) for more than 48 weeks were included. The serum levels of HBV nucleic acids and selected cytokines were measured at 0, 12, 24, and 48 weeks respectively. Results: Serum HBV RNA could still be detected while serum HBV DNA had fallen below the detection limit in patients treated with ETV. There was a strong positive correlation between HBV RNA and HBeAg, with a concomitant decrease in the secretion of cytokines from type 1 helper T (Th1)/type 2 helper T (Th2)/interleu-kin (IL)-17 producing T (Th17) cells. IL-4 and IL-10 were the main cytokines negatively associated with serum HBV RNA. Conclusions: HBeAg can be used to reflect the load of HBV RNA indirectly, because serum HBV RNA has not been widely used in clinical practice. Meanwhile, serum IL-4 and IL-10 might be explored in combination with HBV RNA in guiding future clinical antiviral therapy.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Racial and Health Disparities among Cirrhosis-related Hospitalizations in the USA

    Ashwani K.SingalYong-Fang KuoJuan P.ArabRamon Bataller...
    398-404页
    查看更多>>摘要：Background and Aims: Alcohol-associated liver disease (ALD) is the most common cause of advanced liver disease worldwide, including in the USA. Alcohol use and cirrhosis mortality is higher in American Indian/Alaska Native (AI/AN) compared to Whites. Data are scanty on ALD as a liv-er disease etiology in AI/AN compared to other races and ethnicities. Methods: The National Inpatient Sample on 199,748 cirrhosis-related hospitalizations, 14,241 (2,893 AI/AN, 2,893 Whites, 2,882 Blacks, 2,879 Hispanics, and 2,694 Asians or other races) matched 1:1 for race/ethnic-ity on demographics, insurance, and income quartile of the residence zip code analyzed. Results: After controlling for geographic location and hospital type, odds ratio (OR) and 95％ confidence interval (CI) for ALD as cirrhosis etiology was higher among admissions in AI/AN vs. Whites [1.55 (1.37–1.75)], vs. Blacks [1.87 (1.65–2.11)], vs. Hispanic [1.89 (1.68–2.13)] and Asians/other races [2.24 (1.98–2.53)]. OR was also higher for AI/AN vs. all other races for alcohol-associated hepatitis (AH) as one of the discharge diagnoses. The findings were similar in a subgroup of 4,649 admissions with decompensated cirrhosis and in a cohort of 350 admissions with acute-on-chronic liver failure as de-fined by EASL-CLIF criteria. Alcohol use disorder diagnosis was present in 38％ of admissions in AI/AN vs. 24–30％ in other races, p<0.001. A total of 838 (5.9％) admissions were associated with in-hospital mortality. OR (95％ CI) for in-hospital mortality in AI/AN individuals was 34％ reduced vs. Blacks [0.66 (0.51–0.84)], but no difference was ob-served on comparison with other races. Conclusions: ALD, including AH, is the most common etiology among cirrhosis-related hospitalizations in the USA among AI/AN individuals. In-hospital mortality was observed in about 6％ of admis-sions, which was higher for Blacks and similar in other races compared to admissions for AI/AN. Public health policies should be implemented to reduce the burden of advanced ALD among AI/AN individuals.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Clinical Predictors of Functional Cure in Children 1–6 Years-old with Chronic Hepatitis B

    Jing PanHaiyan WangTiantian YaoXuejiao Liao...
    405-411页
    查看更多>>摘要：Background and Aims: Hepatitis B surface antigen (HB-sAg) clearance is significantly more common in children with chronic hepatitis B (CHB) than in adults; however, the pos-sible influencing factors related to HBsAg loss have yet to be found. This study aimed to explore the efficacy of long-term interferon (IFN)α therapy in treating children with CHB and analyzed the factors influencing functional cure after treat-ment. Methods: A total of 236 children aged 1–6 years and diagnosed with CHB via liver biopsy were included in the study, all receiving IFNα treatment (IFNα-2b monotherapy, IFNα-2b followed by lamivudine [LAM] or IFNα-2b combined with LAM) and followed up for 144 weeks. A comprehen-sive analysis was conducted on clinical data, including bio-chemical items, serum markers of hepatitis B virus (HBV) and immunological indexes, and logistic regression analysis was used to screen the influencing factors related to HB-sAg loss. Results: The cumulative loss rates of HBsAg were 79.5％, 62.1％ and 42.1％ at 144 weeks after the start of treatment in the 1–3 years-old group, 3–5 years-old group and 5–7 years-old group, respectively (p<0.05). IFNα-2b combined with LAM treatment displayed the highest HBsAg loss rates compared with monotherapy and sequential treat-ment (p=0.011). Younger baseline age and lower HBsAg lev-els were independent factors for the prediction of HBsAg loss (p<0.05). The baseline PreS1 and hepatitis B core antibody levels in the HBsAg loss group were lower than those in the HBsAg non-loss group. In addition, the PreS1 level was posi-tively corelated with the level of HBsAg, HBV DNA and liver inflammation. Conclusions: Long-term treatment with IFNα was effective in achieving HBsAg loss in CHB children aged 1–6 years-old. Age less than 3 years-old and lower HBsAg levels are independent predictors of functional cure in chil-dren with CHB.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Advantages of a Novel Model for Predicting Hepatic Fibrosis in Chronic Hepatitis B Virus Carriers Compared with APRI and FIB-4 Scores

    Na-Ling KangQing-Fa RuanDe-Sheng ZhangXue-Ping Yu...
    412-419页
    查看更多>>摘要：Background and Aims: Aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are widely used to assess liver fibrosis in chronic hepatitis B virus (HBV) infection. Currently, the definition of normal alanine aminotransferase (ALT) is controversial. We aimed to exam-ine the diagnostic value of APRI and FIB-4 in chronic HBV carriers with different upper limits of normal (ULNs) for ALT. Methods: 581 chronic HBV carriers were divided into the fol-lowing four groups based on different ULNs for ALT: chronic HBV carriers I,Ⅱ,Ⅲ, and IV. Furthermore, 106 chronic HBV carriers formed an external validation group. Predictive val-ues of APRI and FIB-4 were elucidated using the area un-der the curve (AUC). A liver fibrosis-predictive model-GPSA (named for its measure of gamma glutamyl transpeptidase, platelet count, HBsAg and albumin) was developed using multivariate logistic regression analysis. Results: In chronic HBV carriers I, the AUCs of APRI and FIB-4 were 0.680 and 0.609 for significant fibrosis and 0.678 and 0.661 for cir-rhosis, respectively. The AUCs of GPSA for significant fibrosis in the training group, internal group, and external valida-tion group were 0.877, 0.837, and 0.871, respectively. The diagnostic value of GPSA differed among chronic HBV carri-ers I,Ⅱ,Ⅲ, and IV, with AUCs for significant fibrosis being 0.857, 0.853, 0.868, and 0.905 and AUCs for cirrhosis being 0.901, 0.905, 0.886, and 0.913, respectively. GPSA showed a higher diagnostic value than APRI and FIB-4 for predict-ing significant fibrosis in the four groups. Conclusions: The GPSA model allows for accurate diagnosis of liver fibrosis in chronic HBV carriers with different ULN for ALT.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Impact of National Centralized Drug Procurement Policy on Antiviral Utilization and Expenditure for Hepatitis B in China

    Xinyu ZhaoMin LiHao WangXiaoqian Xu...
    420-428页
    查看更多>>摘要：Background and Aims: The National Centralized Drug Pro-curement (NCDP) policy was launched in mainland China in April 2019, with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) being included in the procurement list. We conducted the current study to investigate the impact of the NCDP policy on the utilization and expenditures of antiviral therapy for chronic hepatitis B (CHB) in China. Methods: Procurement records, including monthly purchase volume, expenditure, and price of nucleos(t)ide analogs (NAs), were derived from the National Healthcare Security Administration from April 2018 to March 2021. The changes in volumes and expenditures of the first-line NAs and bid-winning products were calculated. The effects of price, volume, and structure related to drug expenditure were calculated by the Addis and Magrini (AM) Index System Analysis. Results: The purchase volume of NAs significantly increased from 134.3 to 318.3 million DDDs, whereas the expenditure sharply decreased from 1,623.41 to 490.43 million renminbi (RMB) or 241.94 to 73.09 million US dollars (USD). The proportions of first-line NAs rose from 72.51％ (ETV: 69.00％, TDF: 3.51％) to 94.97％ (ETV: 77.42％, TDF: 17.55％). AM analysis showed that the NCDP policy decreased the expenditure of all NAs (S=0.91) but increased that of the first-line NAs in the bid-winning list (S=1.13). Assuming the population size of CHB patients remains stable and a compliance rate of ≥75％, the proportion of CHB patients receiving first-line antiviral therapy would increase from 6.36–8.48％ to 11.56–15.41％. Conclusions: The implementation of the NCDP policy sig-nificantly increased the utilization of first-line NAs for CHB patients at a lower expenditure. The findings provided evi-dence for optimizing antiviral therapy strategy and allocating medical resources in China.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Dermcidin Enhances the Migration, Invasion, and Metastasis of Hepatocellular Carcinoma Cells In Vitro and In Vivo

    Fanghua QiuHuajing LongLu ZhangJieyuan Liu...
    429-438页
    查看更多>>摘要：Background and Aims: Hepatocellular carcinoma (HCC) is a common primary liver neoplasm with high mortality. Dermcidin (DCD), an antimicrobial peptide, has been re-ported to participate in oncogenesis. This study assessed the effects and underlying molecular events of DCD overex-pression and knockdown on the regulation of HCC progres-sion in vitro and in vivo. Methods: The serum DCD level was detected using enzyme-linked immunosorbent assay. DCD overexpression, knockdown, and Ras-related C3 botu-linum toxin substrate 1 (Rac1) rescue were performed in SK-HEP-1 cells using plasmids. Immunofluorescence stain-ing, quantitative PCR, and Western blotting were used to detect the expression of different genes and proteins. Dif-ferences in HCC cell migration and invasion were detected by Transwell migration and invasion assays. A nude mouse HCC cell orthotopic model was employed to verify the in vitro data. Results: The level of serum DCD was higher in patients with HCC and in SK-HEP-1 cells. DCD overexpres-sion caused upregulation of DCD, fibronectin, Rac1, and cell division control protein 42 homologue (Cdc42) mRNA and proteins as well as actin-related protein 2/3 (Arp2/3) pro-tein (but reduced Arp2/3 mRNA levels) and activated Rac1 and Cdc42. Phenotypically, DCD overexpression induced HCC cell migration and invasion in vitro, whereas knockout of DCD expression had the opposite effects. A Rac1 rescue experiment in DCD-knockdown HCC cells increased HCC cell migration and invasion and increased the levels of active Rac1/total Rac1, Wiskott-Aldrich syndrome family protein (WASP), Arp2/3, and fibronectin. DCD overexpression in-duced HCC cell metastasis to the abdomen and liver in vivo.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease

    Gang LiLiang-Jie TangPei-Wu ZhuOu-Yang Huang...
    439-448页
    查看更多>>摘要：Background and Aims: Intra-abdominal visceral fat accu-mulation and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease (NAFLD). We examined whether the relationship between visceral fat ac-cumulation and liver disease severity may be influenced by PNPLA3 rs738409 polymorphism. Methods: The variant of PNPLA3 rs738409 was genotyped within 523 Han individu-als with biopsy-confirmed NAFLD. Visceral fat area (VFA) was measured by bioelectrical impedance. Significant liver fibrosis (SF), defined as stage F ≥2 on histology, was the outcome measure of interest. Results: The distribution of PNPLA3 genotypes was CC: 27.5％, CG: 48.2％, and GG: 24.3％. Higher VFA was associated with greater risk of hav-ing SF (adjusted-odds ratio [OR]: 1.03; 95％ confidence in-terval [CI]: 1.02–1.04, p<0.05), independent of potential confounders. Among subjects with the same VFA level, the risk of SF was greater among carriers of the rs738409 G genotype than among those who did not. Stratified analy-sis showed that PNPLA3 rs738409 significantly influenced the association between VFA and SF. VFA remained signifi-cantly associated with SF only among the rs738409 G-allele carriers (adjusted-OR: 1.05; 95％ CI: 1.03–1.08 for the GG group; and adjusted-OR:1.03; 95％ CI: 1.01–1.04 for the GC group). There was a significant interaction between VFA and PNPLA3 rs738409 genotype (Pinteraction=0.004). Con-clusions: PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult indi-viduals with biopsy-proven NAFLD. Existence of the PNPLA3 rs738409 G allele and VFA interact to increase risk of SF.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Relationship between the Level of Serum Golgi Protein 73 and the Risk of Short-term Death in Patients with ALD-ACLF

    Jingjing TongMingjie YaoXiuying MuLeijie Wang...
    449-457页
    查看更多>>摘要：Background and Aims: As a hepatocellular carcinoma bio-marker, serum Golgi protein 73 (GP73) is reportedly related to inflammation. Acute-on-chronic liver failure (ACLF) is char-acterized by severe systemic inflammation. In this study, we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF (ALD-ACLF). Methods: This retrospec-tive cohort study involved 126 Chinese adults with ALD-ACLF. Baseline serum GP73 level was measured using enzyme-linked immunosorbent assay. Patients were followed-up for 90 d and outcomes were assessed. Data were analyzed using multivariate Cox regression and piecewise linear regression analyses. The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves. Re-sults: The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF. Compared with the lowest tertile, the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortal-ity risk in the fully adjusted model [at 28 days: hazard ratio (HR): 4.29 (0.99–18.54), p=0.0511; at 90 days: HR: 3.52 (1.15–10.79), p=0.0276]. Further analysis revealed a posi-tive linear association. GP73 significantly improved the ac-curacy of the Child-Turcotte-Pugh score, model for end-stage liver disease score, and model for end-stage liver disease-sodium score in predicting short-time prognosis of patients with ALD-ACLF. Conclusions: The serum GP73 level is a sig-nificant predictor of the subsequent risk of death in patients with ALD-ACLF. GP73 improved the predictive value of classic prognostic scores.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普