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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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    Detection of Prognostic Biomarkers for Hepatocellular Carcinoma through CircRNA-associated CeRNA Analysis

    Li HanMaolong WangYuling YangHanlin Xu...
    80-89页
    查看更多>>摘要：Background and Aims: The prognosis of hepatocellular carcinoma (HCC) is extremely poor; therefore, there is an urgent need for novel prognostic molecular biomarkers of HCC. The current investigation utilized circular (circ)RNA-associated competing endogenous (ce)RNAs analysis in order to identify significant prognostic biomarkers of HCC. Methods: CircRNAs and mRNAs that were differentially expressed between normal and HCC tissues were identi-fied. Their respective functions were predicted with Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A nomogram was used for model verification. Results: A ceRNA network composed of differentially expressed circRNAs and mRNAs was con-structed. Significant hub nodes in the ceRNA network were hsa_circ_0004662, hsa_circ_0005735, hsa_circ_0006990, hsa_circ_0018403 and hsa_circ_0100609. By using this in-formation, a prognostic risk assessment tool was developed based on the expressions of seven genes (PLOD2, TARS, RNF19B, CCT2, RAN, C5orf30 and MCM10). Furthermore, multivariate Cox regression analysis revealed risk and T-stage parameters as independent prognostic factors. The nomograms that were constructed from risk and T-stage groups were used to further assess the prediction of HCC patient survival rates. The nomogram, which consisted of risk and T-stage scores assessment models, was found to be an independent factor for predicting prognosis of HCC. Conclusions: Five circRNAs, including hsa_circ_0004662, hsa_circ_0005735, hsa_circ_0006990, hsa_circ_0018403 and hsa_circ_0100609, that may play key roles in the pro-gression of HCC were identified. Seven gene signatures were identified, which were associated with the aforemen-tioned circRNAs, including PLOD2, TARS, RNF19B, CCT2, RAN, C5orf30 and MCM10, all of which were significant genes involved in the pathophysiology of HCC. These genes may be used as a prognosticating tool in HCC patients.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    A Novel Prognostic Biomarker LPAR6 in Hepatocellular Carcinoma via Associating with Immune Infiltrates

    Jian HeMei MengHui Wang
    90-103页
    查看更多>>摘要：Background and Aims: LPAR6 is the most recently deter-mined G protein-coupled receptor of lysophosphatidic acid, and hardly any study has demonstrated the performance of LPAR6 in cancers. We sought to clarify the relationship of LPAR6 to prognosis potential and tumor infiltration im-mune cells in different cancers. Methods: The expression of LPAR6 and its clinical characteristics were evaluated on various databases. The association between LPAR6 and im-mune infiltrates of various types of cancer were investigated via TIMER. Results: We determined that higher LPAR6 ex-pression level was associated with a better overall survival. Additionally, high LPAR6 expression level was significantly associated with better disease-specific survival (DSS) in bladder cancer, and better overall survival (OS)/ progres-sion-free survival (PFS)/ distant metastasis-free survival (DMFS)/ relapse-free survival (RFS) in breast cancer and some other types of cancers. Moreover, LPAR6 significant-ly affects the prognosis of various cancers via The Cancer Genome Atlas (TCGA). Further research exposed that the mRNA level of LPAR6 was positively coordinated with in-filtrating levels of devious immune cells in hepatocellular carcinoma. Conclusions: Our results imply that LPAR6 is associated with prognosis potential and immune infiltration levels in liver cancer. Moreover, LPAR6 expression possibly contributes to the activation of CD8+ T, naive T, effector T cells and natural killer cells and inactivates T regulatory cells, decreases T cell exhaustion and regulate T helper cells in liver cancer. These discoveries imply that LPAR6 could be a novel biomarker of prognosis for indicating progno-sis potential and immune-infiltrating level in hepatocellular carcinoma.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Identification of Expression Pattern and Clinical Significance of the Small Cajal Body-specific RNA SCARNA16 in Hepatocellular Carcinoma

    Sitong ZhangYuan DingZhongquan SunYao Ge...
    104-111页
    查看更多>>摘要：Background and Aims: For high morbidity and mortality, hepatocellular carcinoma (HCC) becomes a major health issue worldwide. Nowadays, numerous non-coding RNAs (ncRNAs) are known to regulate the occurrence and patho-genesis of tumors. Some ncRNAs have also been developed as tumor biomarkers and therapeutic targets. However, the potential function of the small Cajal body-specific RNA (scaRNA) SCARNA16, a newly identified ncRNA, remains to be explored in HCC. Methods: In both HCC cell lines and specimens from 120 enrolled patients, the expression val-ues of SCARNA16 were detected. We divided patients into SCARNA16 high and low expression subgroups, and then analyzed the difference of various clinical characteristics and prognosis data between subgroups. Results: Compared to paired controls, SCARNA16 was significantly down-regulated in HCC cell lines and clinical specimens (p<0.01). Besides, HCC patients with lower SCARNA16 expression commonly presented with larger and more tumor lesions, more ves-sel carcinoma emboli, more capsular invasion and higher TNM stages (p<0.05). Moreover, SCARNA16 expression was negatively correlated with postoperative prognosis of HCC patients in 5-year follow-up, including tumor-free survival (TFS) (median time of low vs. high subgroups: 14 vs. 48 months, p=0.006) and overall survival (OS) (median time of low vs. high subgroups: 39 vs. 52 months, p=0.001). Besides, SCARNA16 acted as an independent prognostic bio-marker in TFS (hazard ratio [HR]: 0.578, 95％ CI: 0.345–0.969, p=0.038) and OS (HR: 0.366, 95％ CI: 0.178–0.752, p=0.006). Conclusions: Low expression patterns of SCAR-NA16 remarkably associated with severe clinical status and poor survival of patients, suggesting that SCARNA16 pos-sesses potency as a novel biomarker for HCC.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Effectiveness of Tenofovir Alafenamide in Chronic Hepatitis B Patients with Normal Alanine Aminotransferase and Positive Hepatitis B Virus DNA

    Wen-Kang GaoYan-Yun ShuYue ChenYan Ai...
    112-119页
    查看更多>>摘要：Background and Aims: With an increasing understanding of hepatitis B, the antiviral indications have been broadening gradually. To evaluate the effectiveness of tenofovir alafena-mide (TAF) in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and detectable hepatitis B virus (HBV) DNA, those who are ineligible for broader anti-viral criteria from the Chinese CHB prevention guide (2019). Methods: A total of 117 patients were recruited and their data were collected from paper or electronic medical records. HBV DNA and liver function were measured at baseline and throughout the 24-week follow-up. The effectiveness end-point was complete virological response. The safety endpoint was the first occurrence of any clinical adverse event during the treatment. Results: Among the 117 patients, 45 had normal ALT as well as detectable HBV DNA and they were not recommended for antiviral therapy according to Chinese Guidelines (2019). After TAF antiviral therapy, the rates of patients who achieved HBV DNA <20 IU/mL at 4, 12 and 24 weeks were 77.1％, 96.7％ and 96.8％ respectively. Among them, the undetectable rates of HBV DNA in patients with low baseline viral load at 4, 12 and 24 weeks were 92.3％, 100％ and 100％, while the rates of those with high baseline viral load were 68.2％, 94.1％ and 94.4％. Compared with 71.4％, 94.4％ and 94.7％ in the high baseline group, the undetectable rates of HBV DNA at 4, 12 and 24 weeks in the low baseline liver stiffness group were 85.7％, 100％ and 100％. There was no statistical significance among the above groups. Conclusions: CHB patients who had normal ALT and detectable HBV DNA and did not meet "CHB prevention guide (2019)", could achieve complete virological response in 24 weeks after antiviral treatment by TAF.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Elevated Liver Enzymes along with Comorbidity Is a High Risk Factor for COVID-19 Mortality: A South Indian Study on 1,512 Patients

    Narayanasamy KrishnasamyKarthick RajendranParimita BaruaArunkumar Ramachandran...
    120-127页
    查看更多>>摘要：Background and Aims: Liver enzyme abnormalities in coronavirus 2019 (COVID-19) are being addressed in the literature. The predictive risk of elevated liver enzymes has not been established for COVID-19 mortality. In this study, we hypothesized that elevated liver enzymes at ad-mission can predict the outcome of COVID-19 disease with other known indicators, such as comorbidities. Methods: This retrospective study included all the consecutive hos-pitalized patients with confirmed COVID-19 disease from March 4th to May 31st, 2020. The study was conducted in Rajiv Gandhi Government General Hospital, Chennai, Ta-mil Nadu, India. We assessed demography, clinical vari-ables, COVID-19 severity, laboratory parameters, and out-come. Results: We included 1,512 patients, and median age was 47 years (interquartile range: 34–60) with 36.9％ being female. Liver enzyme level (aspartate aminotrans-ferase and/or alanine aminotransferase) was elevated in 450/1,512 (29.76％) patients. Comorbidity was present in 713/1,512 (47.16％) patients. Patients with liver enzymes' elevation and presence of comorbidity were older, more frequently hospitalized in ICU and had more severe symp-toms of COVID-19 at the time of admission. Presence of liver enzymes' elevation with comorbidity was a high risk factor for death (OR: 5.314, 95％ CI: 2.278–12.393), as compared to patients with presence of comorbidity (OR: 4.096, 95％ CI: 1.833–9.157). Conclusions: Comorbid-ity combined with liver enzymes' elevation at presentation independently increased the risk of death in COVID-19 by at least 5-fold.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) and Viral Hepatitis

    Xiaolin WangQing Xie
    128-133页
    查看更多>>摘要：A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed in 2020. The change from nonalcoholic fatty liver disease (NAFLD) to MAFLD highlights the metabolic abnormalities that accompany fatty liver. The diagnosis of MAFLD does not require exclusion of secondary causes of liver diseases and alcohol consump-tion. Thus, MAFLD may coexist with other types of liver dis-eases, such as viral hepatitis, a disease that remains the most common cause of liver disease-related death. With the increasing prevalence of MAFLD, patients with coinci-dental MAFLD and viral hepatitis are frequently encountered in clinical practice. In this review, we mainly summarize the mutual relationship between hepatitis B/C and systematic metabolism dysfunction related to MAFLD. We discuss the impact of MAFLD on progression of viral hepatitis and the therapies. Some unaddressed clinical problems related to concomitant MAFLD and viral hepatitis are also identified.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Biomarkers of Metabolic (Dysfunction)-associated Fatty Liver Disease: An Update

    Jawaher AlharthiMohammed Eslam
    134-139页
    查看更多>>摘要：The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) is rapidly increasing and affects up to two billion individuals globally, and this has also resulted in increased risks for cirrhosis, hepatocellular carcinoma, and liver transplants. In addition, it has also been linked to extrahepatic consequences, such as cardiovascular disease, diabetes, and various types of cancers. However, only a small proportion of patients with MAFLD develop these com-plications. Therefore, the identification of high-risk patients is paramount. Liver fibrosis is the major determinant in de-veloping these complications. Although, liver biopsy is still considered the gold standard for the assessment of patients with MAFLD. Because of its invasive nature, among many other limitations, the search for noninvasive biomarkers for MAFLD remains an area of intensive research. In this review, we provide an update on the current and future biomarkers of MAFLD, including a discussion of the associated genetics, epigenetics, microbiota, and metabolomics. We also touch on the next wave of multiomic-based biomarkers.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Therapeutic Value of Estrogen Receptor α in Hepatocellular Carcinoma Based on Molecular Mechanisms

    Xiangzhe MengXue Liu
    140-146页
    查看更多>>摘要：The incidence of hepatocellular carcinoma (HCC) is signifi-cantly lower in women than men, implying that estrogen receptors (ERs) may play an important role in this sex di-morphism. Recently, considerable progress has been made in expanding our understanding of the mechanisms of ERs in HCC. As one of the most important ERs, ERα functions as a tumor suppressor in the progression of HCC through various pathways, such as STAT3 signaling pathways, lipid metabolism-related signaling pathways, and non-coding RNAs. However, the function of ERα was reduced with the changes of some molecules in the liver, which may develop further into HCC and make it difficult to achieve an effective hormone treatment effect. Intriguingly, there are signs that individualized hormone therapy according to the activity of ERα will overcome this challenge. Based on these observa-tions, it is particularly imperative to reassess and extend the function of ERα. In this review, we mainly elucidated molecular mechanisms associated with ERα in HCC and investigated the individualized hormone therapy based on these mechanisms, with the aim of providing new insights for HCC treatment.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Treatments of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: Current Status and Controversy

    Zhu-Jian DengLe LiYu-Xian TengYu-Qi Zhang...
    147-158页
    查看更多>>摘要：The proportions of patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) varies greatly in different countries or regions, ranging from 13％ to 45％. The treatment regimens for PVTT recommended by HCC guidelines in different countries or regions also vary greatly. In recent years, with the progress and development of surgical concepts, radiotherapy techniques, systematic therapies (for example, VEGF inhibitors, tyrosine kinase in-hibitors and immune checkpoint inhibitors), patients with HCC involving PVTT have more treatment options and their prognoses have been significantly improved. To achieve the maximum benefit, both clinicians and patients need to think rationally about the indications of treatment modalities, the occurrence of severe adverse events, and the optimal fit for the population. In this review, we provide an update on the treatment modalities available for patients with HCC in-volving PVTT. Trials with large sample size for patients with advanced or unresectable HCC are also reviewed.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Persistently Rising Alpha-fetoprotein in the Diagnosis of Hepatocellular Carcinoma: A Review

    Alla TurshudzhyanGeorge Y.Wu
    159-163页
    查看更多>>摘要：Hepatocellular carcinoma (HCC), one of the most common malignant tumors worldwide, is known for its grim prog-nosis, with untreated life expectancy being only a matter of months after the diagnosis. The difficulty in making a diagnosis early is one of the main contributing factors to the poor prognosis. Alpha-fetoprotein (AFP) had long been used as a surveillance tool, but suboptimal specificity and sensitivity has prompted liver societies to abandon the rec-ommendation for its universal use, even in combination with ultrasonography. Most studies have shown no obvi-ous correlation between serum AFP level and HCC tumor size, stage, or survival post-diagnosis. However, some stud-ies concluded that a gradual rise or persistent elevation in AFP were positive predictors for tumor development. Other studies reported a fall in AFP followed by a rise in patients with HCC as well as persistently rising AFP levels without development of HCC on follow up. Our calculation of the sensitivity and specificity of persistently rising AFP for HCC were both low, at 60％ and 35.8％, respectively, indicating that the presence of persistently rising AFP per se did not offer diagnostic benefit. In addition, our calculated mean slopes of persistently rising AFP levels in HCC and non-HCC patients were numerically very different, but the difference was not statistically significant. We conclude that the pub-lished data do not support a role for rising AFP levels per se in the diagnosis of HCC.
      原文链接:
    • NETL
    • NSTL
    • 万方数据