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Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma. 全面回顾胆汁淤积性肝损伤和胆管癌的分子机制
Pub Date : 2018-01-01 Epub Date: 2018-09-20 DOI: 10.4172/2167-0889.1000231
Shohaib Virani, Austin Akers, Kristen Stephenson, Steven Smith, Lindsey Kennedy, Gianfranco Alpini, Heather Francis

Cholestatic liver injury is characterized by damage induced on the biliary tree and cholangiocytes, the cells lining the biliary tree, thus they are termed "cholangiopathies". Cholangiopathies include diseases such as Primary Biliary Cholangitis, Primary Sclerosing Cholangitis, Biliary Atresia and Cholangiocarcinoma. These pathologies lack viable therapies and most patients are diagnosed during late stage disease progression (with the exception of Biliary Atresia, which is found shortly after birth). The lack of therapies for these diseases has put a significant burden on the need for liver transplantation as this is the only indicative "cure" for cholangiopathies. The molecular mechanisms for cholangiopathies have been extensively studied; however, and unfortunately, the lack of effective biomarkers and therapeutics remains. In this review article we highlight the latest studies to investigate the molecular mechanisms regulating cholangiopathies and the potential therapeutics that might be discovered.

胆汁淤积性肝损伤的特点是对胆道树和胆管细胞(胆道树的内衬细胞)造成损伤,因此被称为 "胆道疾病"。胆道疾病包括原发性胆管炎、原发性硬化性胆管炎、胆道闭锁和胆管癌等疾病。这些病症缺乏可行的疗法,大多数患者都是在疾病发展到晚期时才被诊断出来的(胆道闭锁除外,这种疾病在患者出生后不久就会被发现)。由于缺乏针对这些疾病的治疗方法,肝脏移植成为胆道疾病唯一可以 "治愈 "的方法,这给肝脏移植的需求带来了沉重负担。人们对胆道疾病的分子机制进行了广泛的研究,但遗憾的是,仍然缺乏有效的生物标志物和疗法。在这篇综述文章中,我们将重点介绍调控胆道疾病分子机制的最新研究以及可能发现的潜在疗法。
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引用次数: 0
Hepatic Anisakiasis in Japan 日本的肝异尖线虫病
Pub Date : 2018-01-01 DOI: 10.4172/2167-0889.1000230
T. Shizuma
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引用次数: 0
Retrospective Comparative Study of Spontaneous Peritonitis Associated with Fungal and Bacterial Infection in Patients with Liver Cirrhosis 肝硬化患者自发性腹膜炎并发真菌和细菌感染的回顾性比较研究
Pub Date : 2018-01-01 DOI: 10.4172/2167-0889.1000226
T. Shizuma
Objective: Although patients with liver cirrhosis (LC) have a high risk of developing bacterial and fungal infections, few studies have evaluated spontaneous fungal peritonitis (SFP) or fungiascites in this population. Accordingly, we conducted a retrospective comparative study of spontaneous peritonitis associated with fungal (SFP and fungiascites) or bacterial culture-positive ascites [spontaneous bacterial peritonitis (SBP) and bacterascites] in patients with LC.Methods: This study enrolled 73 patients with LC and ascitic culture-positive spontaneous peritonitis, including four, three, 35, and 31 patients with SFP, fungiascites, culture-positive SBP, and bacterascites, respectively. We compared the laboratory findings, Child–Pugh scores, and 1-month mortality rates between patients with fungal disease, i.e., spontaneous peritonitis associated with fungal culture-positive ascites (SFP and fungiascites), and those with bacterial disease, i.e., spontaneous peritonitis associated with bacterial culture-positive ascites (culturepositive SBP and bacterascites).Results: We observed no significant differences in the severity of underlying liver dysfunction and renal impairment between patients with fungal and bacterial disease. However, the 1-month mortality rate was significantly higher in patients with fungal disease than in those with bacterial disease (71.4%, 5/7 vs. 25.8%, 17/66; p= 0.038).Conclusion: In our retrospective study population, spontaneous peritonitis caused by fungi (SFP and fungiascites) was associated with a significantly higher short-term mortality rate compared with that of spontaneous peritonitis caused by bacteria (culture-positive SBP and bacterascites). Further studies are required to investigate the underlying mechanisms and determine the effects of antifungal therapy on mortality.
目的:尽管肝硬化(LC)患者发生细菌和真菌感染的风险很高,但很少有研究评估该人群的自发性真菌性腹膜炎(SFP)或真菌腹水。因此,我们对LC患者自发性腹膜炎合并真菌(SFP和真菌腹水)或细菌培养阳性腹水[自发性细菌性腹膜炎(SBP)和细菌腹水]进行了回顾性比较研究。方法:本研究纳入73例LC和腹水培养阳性的自发性腹膜炎患者,其中SFP、真菌腹水、培养阳性SBP和细菌腹水分别为4例、3例、35例和31例。我们比较了真菌性疾病(即自发性腹膜炎合并真菌培养阳性腹水(SFP和真菌腹水))和细菌性疾病(即自发性腹膜炎合并细菌培养阳性腹水(SBP和细菌腹水培养阳性))患者的实验室检查结果、Child-Pugh评分和1个月死亡率。结果:我们观察到真菌和细菌性疾病患者潜在的肝功能障碍和肾功能损害的严重程度没有显著差异。然而,真菌病患者的1个月死亡率明显高于细菌性疾病患者(71.4%,5/7 vs. 25.8%, 17/66;p = 0.038)。结论:在我们的回顾性研究人群中,与细菌(培养阳性的SBP和细菌腹水)引起的自发性腹膜炎相比,真菌(SFP和真菌腹水)引起的自发性腹膜炎的短期死亡率明显更高。需要进一步的研究来调查潜在的机制并确定抗真菌治疗对死亡率的影响。
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引用次数: 2
Liver Function Tests in Normal Pregnant Women 正常孕妇肝功能检查
Pub Date : 2018-01-01 DOI: 10.4172/2167-0889.1000228
D. Mutua, E. Njagi, G. Orinda
Changes in liver function tests (LFTs) are normal during pregnancy. However, severe liver disease, although rare, can occur and must be recognized at an early stage to reduce maternal and fetal morbidity and mortality. It is important to differentiate between normal physiological changes and disease pathology. This review highlights the important LFT changes that take place during normal pregnancy.
妊娠期间肝功能检查(LFTs)的变化是正常的。然而,严重的肝脏疾病,虽然罕见,但可能发生,必须在早期阶段发现,以减少产妇和胎儿的发病率和死亡率。区分正常的生理变化和疾病病理是很重要的。本综述强调了正常妊娠期间发生的重要LFT变化。
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引用次数: 12
Radiological Patterns of Hepatocellular Cancers Vis-Ã-Vis Histopathological Differentiation: A Radiological Appraisal 肝细胞癌的影像学表现-Ã-Vis组织病理分化:影像学评价
Pub Date : 2018-01-01 DOI: 10.4172/2167-0889.1000224
K. Razak, Surbhi Gupta, Meena Gl
Aims and Objectives: The objective of our study is to determine the degree of radio-pathological correlation of HCC according to our experience at our institution. Methods: Radiological parameters: All patients underwent a dynamic imaging study by CT and/or MRI, including at least one image acquisition in the arterial phase and another in the portal phase. Pathological parameters: The 63 patients presented histological confirmation of HCC, obtained by means of a biopsy with a thick needle of 18 G or in a surgical specimen. In all of them, the histological grade of the tumor was assessed according to the WHO classification, which distinguishes 4 grades: well differentiated (BD), moderately differentiated (MD), poorly differentiated (PD) and undifferentiated. These last two were grouped into a single group. Conclusion: Characteristics of HCC helps in the estimation of the histological grade: arterial phase enhancement, washing, heterogeneity of the lesions, regularity of the contours and the presence of fat deposits and intratumoral vessels.
目的和目的:我们研究的目的是根据我们在本机构的经验确定HCC的放射病理相关程度。放射学参数:所有患者均通过CT和/或MRI进行动态成像研究,包括至少一幅动脉期和另一幅门静脉期的图像采集。病理参数:63例患者通过18 G粗针活检或手术标本获得HCC组织学证实。所有病例均按WHO分级进行肿瘤组织学分级,分为高分化(BD)、中分化(MD)、低分化(PD)、未分化4个级别。后两者被归为一组。结论:HCC的特点有助于组织学分级的估计:动脉期增强、清洗、病变的异质性、轮廓的规律性、脂肪沉积和肿瘤内血管的存在。
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引用次数: 0
Assessment of Quality of Life of Hepatitis C Patients Treated By Sovaldi Drug in Viral Hepatitis Treatment Center in Ismailia Fever Hospital, Egypt 埃及伊斯梅利亚发热医院病毒性肝炎治疗中心Sovaldi治疗丙型肝炎患者的生活质量评价
Pub Date : 2018-01-01 DOI: 10.4172/2167-0889.1000233
Ezzat El Niwehy, A. Hany, A. F. Mohamed, E. Moubarak, Esraa Ayed, M. Mousa, Merna Abd Elatif, Omar Mohamed, Reham H Mohamed, Reham Farid, S. Soliman, Hussien A. Amer
Introduction: patients with chronic liver disease are suffering from fatigue, loss of self-esteem, inability to function at work, anxiety, depression, and other emotional problems that profoundly decrease their quality of life and well-being. Objectives: To assess the quality of life of hepatitis C patients receiving Sovaldi drug. To determine most common short-term side effects of Sovaldi containing regimen medication. Methods: A descriptive cross sectional study was carried out in Viral Hepatitis Treatment Center Ismailia fever Hospital. Study population was Hepatitis c virus patients treated with regimen containing sovaldi (sovaldi+ribavirin for 12 weeks). Simple random sampling was used to select the subjects included in the study Using sample size ready-made tables, 74 patients were selected to participate in this study where an interviewing questionnaire used to collect the data by 36 RAND questionnaire. Results: About 49% of the patients noticed change in their mode to the worst, and 5% felt depressed to the extent of suicide and about 61% of the patients were having difficulty with sleeping and concentrating. About half of the patients (50%) were having poor role-emotional. the most common short-term side effect were Headache which was the highest (53%) while others as(joint pain-decreasing sexual function-decreasing appetite) followed it. 35.2% were having excellent social functioning during the period of treatment of sovaldi, whereas (about 56.8%) ranging from poor to fair social functioning. Conclusion: the study was carried on 74 patients and the results were controversial as regarding their lifestyle affection, some people got better and others got worse especially those experienced recurrence of the disease. We recommend larger studies with large sample size to detect effectively the life style changes with medication.
慢性肝病患者患有疲劳、丧失自尊、无法工作、焦虑、抑郁和其他情绪问题,这些问题严重降低了他们的生活质量和幸福感。目的:评价接受索伐地治疗的丙型肝炎患者的生活质量。确定索伐地含方案用药最常见的短期副作用。方法:在伊斯梅利亚发热医院病毒性肝炎治疗中心进行描述性横断面研究。研究人群为丙型肝炎病毒患者,使用sovaldi (sovaldi+利巴韦林治疗12周)。本研究采用简单随机抽样的方法选取研究对象,采用样本量现成表格,选取74例患者参与本研究,采用访谈问卷,采用36份RAND问卷收集数据。结果:约49%的患者意识到自己的生活方式发生了变化,达到了最坏的状态,5%的患者感到抑郁到自杀的程度,约61%的患者出现了睡眠困难和注意力不集中的情况。大约一半的患者(50%)的角色情绪不佳。最常见的短期副作用是头痛,最高(53%),其次是其他副作用(关节疼痛、性功能减退、食欲减退)。在sovaldi治疗期间,35.2%的患者社会功能良好,而56.8%的患者社会功能从差到一般。结论:该研究对74例患者进行了研究,结果存在争议,关于他们的生活方式的影响,有些人好转,有些人恶化,特别是那些经历过疾病复发的人。我们建议进行更大规模的研究,样本量更大,以有效地检测药物对生活方式的改变。
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引用次数: 2
Persistent Ascites after Orthotopic Liver Transplantation: Analysis of Predictive Factors 原位肝移植术后持续腹水:预测因素分析
Pub Date : 2018-01-01 DOI: 10.4172/2167-0889.1000232
M. Mucenic, A. Brandão, C. Marroni, Alfeu M. Fleck-Junior, M. L. Zanotelli, G. Cantisani
Objective: Long-term persistence of ascites after orthotopic liver transplant can impact significantly on postoperative morbidity. Previous studies disclosed varied results in regard to prevalence, risk factors, ascitic fluid analysis and prognosis. The objective of the present study was to ascertain prevalence and risk factors in order to have a better understanding of this complication. Methods: All orthotopic liver transplantations performed for three consecutive years were considered for inclusion. The outcome was defined as ascites that was evident on clinical examination and/or required the use of diuretics for more than 90 days after surgery. Results: The main indications for transplant were decompensated cirrhosis and hepatocellular carcinoma. Ascites persisted in 19 (13.67%) out of 139 cases. Predictive factors were portosystemic encephalopathy, portal vein thrombosis, splenomegaly, creatinine level and volume of ascites drained during surgery. On multiple regression analysis, only the amount of ascites drained during transplantation (5.05 L × 1.58 L; p<0.008) and creatinine levels less than 12 hours before transplantation (2.39 mg/dL × 1.22 mg/dL; p=0.018) remained significantly related to ascites persistence. All biochemical analysis revealed increased serum-ascites albumin gradient. Death in the first year was similar in patients with or without ascites persistence (5.6 × 4.3%) Conclusion: This study evaluated multiple potential risk factors that could contribute to long-term persistence of ascites after liver transplantation. Loss of renal function and greater volume of ascites were significantly related to persistent ascites, which was a transudate with increased serum-ascites albumin gradient. Persistent ascites was not associated with increased mortality.
目的:原位肝移植术后腹水长期存在对术后发病率有显著影响。以往的研究揭示了关于患病率、危险因素、腹水分析和预后的不同结果。本研究的目的是确定患病率和危险因素,以便更好地了解这种并发症。方法:纳入所有连续3年的原位肝移植。结果定义为临床检查明显的腹水和/或术后需要使用利尿剂超过90天。结果:失代偿性肝硬化和肝癌是肝移植的主要适应症。139例腹水持续19例(13.67%)。预测因素为门系统脑病、门静脉血栓形成、脾肿大、肌酐水平和术中排出的腹水量。在多元回归分析中,只有移植过程中排出的腹水量(5.05 L × 1.58 L;p<0.008),移植前12小时肌酐水平(2.39 mg/dL × 1.22 mg/dL;P =0.018)仍与腹水持续存在显著相关。所有生化分析均显示血清-腹水白蛋白梯度升高。结论:本研究评估了可能导致肝移植术后腹水长期存在的多种潜在危险因素。肾功能丧失和腹水体积增大与持续性腹水显著相关,这是一种血清-腹水白蛋白梯度升高的漏出现象。持续腹水与死亡率增加无关。
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引用次数: 2
Quantification of Hepatic Lipid Using 7.0T Proton Magnetic Resonance Spectroscopy and Computed Tomography in Mild Alcoholic Steatotic Mice. 利用 7.0T 质子磁共振波谱和计算机断层扫描对轻度酒精性脂肪肝小鼠的肝脂进行定量分析
Pub Date : 2018-01-01 Epub Date: 2018-12-31 DOI: 10.4172/2167-0889.1000234
Qi Cao, Su Xu, Shujing Li, Minjie Chen, Xicui Sun, Yamin Wan, Liya Pi, Zhekang Ying, Bin Ren

Background: In vivo proton magnetic resonance spectroscopy (1H MRS) has been used to semi-quantify hepatic lipids in preclinical and clinical studies of fatty liver disease. Quantifying absolute amount of liver lipids utilizing 1H MRS and computerized tomography (CT) is essential to accurately interpret hepatic steatosis.

Purpose: To establish reliable parameters to convert relative hepatic lipid levels obtained by 1H-MRS and liver volumes by CT to the absolute amount of liver lipids in a mild hepatic steatosis, and to determinate the correlation between these absolute liver lipids with liver triglyceride (TG) and cholesterol (Chol) measured by biochemistry assays.

Methods: Mild steatosis was induced in mice by a 3 week ethanol diet containing standard lipids. Evaporated liver water was measured after baking liver tissues and volume of liver was measured using water displacement. 1H MRS semiquantitation of hepatic lipids and CT measurement of liver volume were performed and then used to calculate amount of liver lipids. These data were compared with liver TG and Chol.

Results: Percentage of liver water and liver density were persistent in two groups and were used to convert the percentage of liver lipids to liver water by 1H-MRS to the absolute amount of liver lipids per gram of liver or per milliliter of CT volume. Using 1H-MRS and biochemical assays, an increase of liver lipids was confirmed in mild steatosis mice compared to controls (P<0.01). The amounts of imaging detected liver lipids were strongly correlated to liver TG and Chol measured by biochemical assays in mild steatosis mice.

Conclusion: 1H MRS and CT liver imaging techniques are able to quantify absolute hepatic lipid levels utilizing relative persistent parameters percentage of liver water and liver density in a preclinical mild steatosis setting.

背景:在脂肪肝的临床前和临床研究中,体内质子磁共振波谱(1H MRS)已被用于对肝脏脂质进行半定量分析。目的:建立可靠的参数,将 1H-MRS 获得的相对肝脂水平和 CT 测得的肝脏体积转换为轻度肝脂肪变性中肝脂的绝对量,并确定这些绝对肝脂与生化测定法测得的肝甘油三酯 (TG) 和胆固醇 (Chol) 之间的相关性:方法:用含标准脂质的乙醇饮食诱导小鼠患轻度脂肪肝,为期 3 周。烘烤肝组织后测量肝脏蒸发的水分,并使用水置换法测量肝脏体积。对肝脏脂质进行 1H MRS 半定量分析,并对肝脏体积进行 CT 测量,然后用于计算肝脏脂质的含量。这些数据与肝脏的总胆固醇和胆固醇进行了比较:结果:两组患者的肝水百分比和肝脏密度持续存在,并通过 1H-MRS 将肝脂占肝水的百分比转换为每克肝脏或每毫升 CT 容量的肝脂绝对量。通过 1H-MRS 和生化检测,证实与对照组相比,轻度脂肪变性小鼠的肝脏脂质有所增加(结论:1H MRS 和 CT 肝脏成像技术能够在临床前轻度脂肪变性的情况下,利用肝水和肝脏密度的相对持久参数百分比来量化肝脏脂质的绝对水平。
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引用次数: 0
Impact of Age on Survival after Partial Portal Vein Arterialization for the Treatment of Post-Hepatectomy Liver Failure in a Rat Model 年龄对部分门静脉动脉化治疗肝切除术后肝衰竭大鼠模型存活的影响
Pub Date : 2017-09-28 DOI: 10.4172/2167-0889.1000221
M. Novello, Aless, R. Zullo, L. Niccoli, Michele Ruggiero, Raffaele Gr, M. Cannistra', M. FrancescoVito, arino, L. Puviani, G. Cavallari, B. Nardo
Introduction: Post-operative liver failure (PLF) occurs in approximately 10% of patients undergoing major hepatectomy. Partial portal vein arterialization (PPVA) enhances the regenerative capacity of the resected liver. The aim of this study was to investigate the impact of age on survival after PPVA for the treatment of post-operative liver failure in a rat model. Materials and Methods: 24 rats underwent extended liver resection, that leaded to PLF. 12 rats were divided in 2 groups treated with PPVA: group 1a-young rats (n=6, age 2 months) and group 2a-old rats (n=6, age 30 months). Two control groups of rats of the same age were not treated with PPVA: group 1b-young and group 2b-old. Results: on postoperative day 7, no significant differences were observed among all groups in terms of ALT levels, prothrombin activity and serum creatinine. As for the liver regeneration markers, the level of mitotic index was greater in the groups treated with PPVA compared to the control groups (without significant differences between young and old groups). The 75% (9/12) of the rats treated with PPVA survived up to 7 days, with no significant differences between young (5/6) and elderly rats 66.7% (4/6). Conclusion: PPVA treatment had the same beneficial effect both in young and old rats.
导言:大约10%的大肝切除术患者发生术后肝衰竭(PLF)。部分门静脉动脉化(PPVA)增强了切除肝脏的再生能力。本研究的目的是探讨年龄对PPVA治疗术后肝衰竭大鼠模型后生存的影响。材料与方法:24只大鼠行大面积肝切除,导致PLF。将12只大鼠分为2组:a-幼龄组(n=6,年龄2月龄)和2a-老年组(n=6,年龄30月龄)。相同年龄的两组大鼠不给予PPVA治疗:1b-young组和2b-old组。结果:术后第7天,各组间ALT水平、凝血酶原活性、血清肌酐均无显著差异。肝再生标志物方面,PPVA处理组有丝分裂指数水平高于对照组(青年组与老年组无显著差异)。75%(9/12)的大鼠经PPVA处理后存活达7天,与年轻大鼠(5/6)和老年大鼠(66.7%(4/6)无显著差异。结论:PPVA治疗对年轻大鼠和老年大鼠均有相同的有益效果。
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引用次数: 0
The Function and Application of 3D Visualization in the Treatment of Primary Hepatic Carcinoma 三维可视化在原发性肝癌治疗中的作用及应用
Pub Date : 2017-09-28 DOI: 10.4172/2167-0889.1000223
X. Hao, C. Jiajia
Primary Hepatic Carcinoma refers to malignant liver tumors. Hepatocellular Carcinoma accounts for more than 90% of primary hepatic carcinomawith its incidence rate ranking the sixth in global tumor incidence and mortality rate ranking the third in tumor-related death in the world. Surgical resection is the preferred treatment for early primary hepatic carcinoma. It includes liver transplantation, partial hepatectomy, laparoscopic hepatectomy, etc. based on Milan criteria, University of California criteria and Hang Zhou criteria. But how the operation is done relies on tumor-evaluation in different stages before the surgery. Medical Imaging is the way to evaluate malignancy degree but is usually 2D. Even though the high-end CT and MR can reconstruct 3D image, clinicians are still provided with 2D image. Therefore, in order to diagnose diseases, surgeons have to reconstruct 2D image into 3D image in their mind according to their experience and liver anatomical structure, causing possible uncertainty and errors in the treatment [1]. It is more so in the following cases: complicated hepatectomy, which requires to resect a larger part of liver tissue, may give rise to postoperative hepatic disorder or even hepatic failure; special surgery site makes it hard to expose the anatomical position and may cause intraoperative bleeding because it is close to major vessels; hepatic blood supply disorder (hepatic congestion, hepatic ischemia) increases difficulty and risk in surgery. All of the above require clinicians to make sufficient preoperative plans, careful intraoperative anatomy and proper postoperative management [2].
原发性肝癌是指肝脏恶性肿瘤。肝细胞癌占原发性肝癌的90%以上,其发病率在全球肿瘤发病率中排名第六,死亡率在肿瘤相关死亡中排名第三。手术切除是早期原发性肝癌的首选治疗方法。根据米兰标准、美国加州大学标准和杭州标准,包括肝移植、肝部分切除术、腹腔镜肝切除术等。但如何进行手术取决于手术前不同阶段的肿瘤评估。医学影像学是评估恶性程度的方法,但通常是二维的。尽管高端的CT和MR可以重建三维图像,但临床医生仍然只能看到二维图像。因此,为了诊断疾病,外科医生必须根据自己的经验和肝脏解剖结构,在脑海中将二维图像重建为三维图像,这可能会导致治疗的不确定性和错误[1]。在以下情况下更是如此:复杂的肝切除术,需要切除更大的肝组织,可能导致术后肝功能紊乱甚至肝功能衰竭;特殊手术部位靠近大血管,解剖位置不易暴露,易引起术中出血;肝血供紊乱(肝充血、肝缺血)增加手术难度和风险。所有这些都需要临床医生制定充分的术前计划,仔细的术中解剖和适当的术后管理bbb。
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引用次数: 0
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Journal of Liver
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